Wallach / Feldmann / Kovalenko Advances in TNF Family Research

Proceedings of the 12th International TNF Conference, 2009
1. Auflage 2010
ISBN: 978-1-4419-6612-4
Verlag: Springer US
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, Band 691, 844 Seiten, eBook

Reihe: Advances in Experimental Medicine and Biology

The biennial TNF-family conferences have been held over the past 20 years, from the time that TNF was cloned. These meetings have followed the enormous progress in this field. Much is now known about the members of the TNF ligand and receptor families, their signaling proteins, mechanisms of action and cellular functions. This volume is the proceedings of the 12th TNF International Conference, held in April 2009. This conference focuses on the physiological, pathophysiological, and medical significance of these important regulators. Sessions at the meeting specifically address their involvement in immunity, development, apoptosis, autoimmunity, cancer, and infection, the normal function and pathology of the neuronal system, as well as major unresolved questions about their mechanisms of action.

Zielgruppe

Research

Autoren/Hrsg.

Feldmann, Marc

Kovalenko, Andrew

Wallach, David

Inhaltsverzeichnis

1;Preface by David Wallach;4
1.1; The Biennial International TNF Conferences and Their Proceedings;4
1.2; References;7
2;Preface by Marc Feldmann;8
2.1; Introduction;8
2.1.1; The TNF/TNF-R Family: A Gold Mine for Clinical Therapeutic Targets?;8
2.2; Reference;9
3;Contents;11
4;Contributors;19
5;Part I Roles of the TNF Family in Tissue Homeostasis and Normal Development;35
5.1;1 Workshop Summary: Roles of the TNF Family in Normal Development and Cancer ;36
5.2;2 TNF Conference 2009: Beyond Bones RANKL/RANK in the Immune System;38
5.2.1; The Role of the RANKLRANKOPG Axis in Bone Remodeling;38
5.2.2; RANKLRANK Signaling in the Immune System;39
5.2.2.1; Lymph Node Development;39
5.2.2.2; RANKL--RANK Signaling in T-Cell--Dendritic Cell Interactions;40
5.2.2.3; RANKL0RANK Control the Development of AIRE+ Medullary Epithelial Cells;42
5.2.2.4; RANKL--RANK Signaling in UV-Induced Immunosuppression;44
5.2.2.5; Functions of RANKL--RANK in Extramedullary Hematopoiesis and B Cells;45
5.2.3; RANKLRANK Signaling, T Cells and Bone Loss The Foundation of Osteoimmunology;46
5.2.4; RANKLRANK Are the Molecular Triggers of Bone Loss in Arthritis;47
5.2.5; RANKL Inhibition as a New Therapy to Control Bone Loss in Human Patients;50
5.2.6; Conclusions;50
5.2.7;References;51
5.3;3 The Edar Subfamily in Hair and Exocrine Gland Development;56
5.3.1; Introduction;56
5.3.2; Conservation of the Edar Subfamily;56
5.3.3; Edar Subfamily in Hair Follicle Development;57
5.3.3.1; Intricate Interplay Between Edar and Wnt Pathways Regulates Hair Development;58
5.3.3.2; Transcriptional Targets of Edar;59
5.3.3.3; Functional Redundancy Between Troy and Edar;60
5.3.4; Edar Subfamily in Glandular Appendages;61
5.3.4.1; Mammary Gland Development;62
5.3.5; Concluding Remarks;63
5.3.6;References;63
5.4;4 High Endothelial Venule Reporter Mice to Probe Regulation of Lymph Node Vasculature;67
5.4.1; Introduction;67
5.4.2; Materials and Methods;69
5.4.2.1; Mice;69
5.4.2.2; Immunization with Oxazolone;70
5.4.2.3; Development of HEC6ST-GFP Reporter Mice;70
5.4.2.4; Immunofluorescence Analysis;71
5.4.3; Results and Discussion;71
5.4.3.1; Vessels Positive for Markers of both HEVs and LVs Are Apparent After Immunization;71
5.4.3.2; HEC6ST-eGFP Mice Have Been Developed;72
5.4.3.3; HEC6ST-eGFP Mice Recapitulate Endogenous HEC6ST Expression;74
5.4.4;References;75
5.5;5 Eiger and Wengen: The Drosophila Orthologs of TNF/TNFR;77
5.5.1; Identification and Signaling Mechanisms of Eiger;77
5.5.2; Role of Eiger in Epithelial Tumor Suppression;78
5.5.3; Other Physiological Roles of Eiger;80
5.5.3.1; Roles in Host Defense;80
5.5.3.2; Role in Cell Proliferation;81
5.5.3.3; Role in Pain Sensitization;81
5.5.4; Further Genetic Analysis of Eiger Signaling;81
5.5.5;References;81
6;Part II Novel Aspects of Signaling Activation by the TNF Family: Novel Aspects of the Functions of the TRAFs and cIAPs;83
6.1;6 Workshop Summary: Novel Aspects of the Functions of the TRAFs and cIAPs ;84
6.1.1;References;90
6.2;7 TRAF2 and Cellular IAPs: A Critical Link in TNFR Family Signaling;93
6.2.1; Discovery of Cellular IAP Proteins and TRAF2;93
6.2.2; Structural Properties of Cellular IAPs and TRAF2;93
6.2.3; TRAF2 and c-IAP Proteins in Signaling Pathways;96
6.2.4; Regulation of Apoptotic Pathways by c-IAPs and TRAF2;99
6.2.5;Targeting c-IAPs and TRAF2 for Therapeutic Intervention ;101
6.2.6;References;103
6.3;8 New Perspectives in TNF-R1-Induced NF-B Signaling;109
6.3.1; TNF-R1-Induced Activation of Canonical NF-B;109
6.3.2; cIAP1/2 Are Required for RIPK1 Ubiquitylation and NF-B Activation;111
6.3.3; RIPK1 Is Not Required for NF-B Activation;113
6.3.4; Alternative Mechanisms for NF-B Activation;114
6.3.5; NF-B and TNF-Mediated Cell Death;115
6.3.6;References;116
6.4;9 Structural Studies of NEMO and TRAF6: Implications in NF-B Activation;119
6.4.1;References;120
7;Part III Novel Aspects of Signaling Activation by the TNF: Ubiquitin Modification of Signaling Proteins;122
7.1;10 Modification by Single Ubiquitin Moieties Rather Than Polyubiquitination Is Sufficient for Proteasomal Processing of the p105 NF-B Precursor;123
7.1.1; Introduction;123
7.1.2; Results;125
7.1.2.1; Involvement of the Ubiquitin System in Processing of p105;125
7.1.2.2; Processing of p105 Does Not Require Polyubiquitination;125
7.1.2.3; Monoubiquitination(s) Is Sufficient for Processing of p105 In Vivo;128
7.1.2.4; Processing of p105 Requires Multiple Monoubiquitinations;131
7.1.2.5; The 26S Proteasome Binds Multiply Monoubiquitinated p105;131
7.1.3; Discussion;131
7.1.4;References;134
7.2;11 Selective Binding of Linear Ubiquitin Chains to NEMO in NF-kappaB Activation;135
7.2.1; Introduction;135
7.2.2; Main Text;136
7.2.2.1; The NEMO--UBAN Domain Selectively Binds to Linear Ubiquitin Chains;136
7.2.2.2; The NEMO--UBAN Domain Forms a-Helical Dimer;137
7.2.2.3; Determination of Linear-Ubiquitin Binding Surfaces in the NEMO--UBAN Domain;137
7.2.2.4; Role of Linear Ubiquitin Binding to NEMO in Regulation of Signaling;137
7.2.3; Discussion and Future Perspectives;139
7.2.4;References;141
7.3;12 The Linear Ubiquitin Chain Assembly Complex (LUBAC) Forms Part of the TNF-R1 Signalling Complex and Is Required for Effective TNF-Induced Gene Induction and Prevents TNF-Induced Apoptosis;143
7.3.1; Introduction;143
7.3.2; Identification of HOIL-1 and HOIP as Novel Components of the Native TNF-RSC;145
7.3.3; LUBAC Recruitment to the TNF-RSC Is Dependent on TRADD, TRAF2/5, and cIAP1/2;145
7.3.4; HOIL-1 and HOIP Directly Interact with Specific Polyubiquitin Chains;146
7.3.5; HOIL-1 and HOIP Mediate TNF-Induced Signalling Events, Gene Induction, and Protect from TNF-Induced Apoptosis;147
7.3.6; HOIL-1 and HOIP Are Required for Stable TNF-RSC Formation;147
7.3.7; Conclusions;148
7.3.8;References;152
7.4;13 Temporal Control of TNF Signaling by Miz1;155
7.4.1;References;156
8;Part IV Novel aspects of Signaling Activation by the TNF Family: TNF Signaling and Gene Regulatory Networks;157
8.1;14 Large-Scale RNAi Screens to Dissect TNF and NF-B Signaling Pathways;158
8.1.1; Introduction;158
8.1.2; TNF-Induced NF-B Activation;159
8.1.3; TNF/NF-B Signaling: A Link Between Inflammation and Cancer;161
8.1.4; RNAi Screens to Dissect Signaling Pathways;162
8.1.5; Design Principles of Large-Scale RNAi Screens for TNF/NF-B;162
8.1.6; New Targets, New Drugs?;164
8.1.7;References;165
8.2;15 Pathogenic Role of IL-6 Combined with TNF- or IL-1 in the Induction of Acute Phase Proteins SAA and CRP in Chronic Inflammatory Diseases;167
8.2.1; Introduction;167
8.2.2; Contribution of Cytokines to the Pathogenesis of RA;167
8.2.2.1; In Vitro SAA Induction Mechanism;168
8.2.3; In Vitro CRP Induction Mechanism;171
8.2.4; Inhibition of SAA and CRP Production by IL-6 Blockade Both In Vitro and In Vivo;172
8.2.5; Pathogenic Role of IL-6 Combined with TNF- or IL-1 on the Induction of SAA and CRP in RA Based on Evidence Obtained from In Vitro Experiments;174
8.2.6;References;175
8.3;16 Understanding Life and Death at CD95;177
8.3.1; Introduction;177
8.3.2; Results and Discussion;180
8.3.3; Materials and Methods;184
8.3.3.1; Cell Lines;184
8.3.3.2; Antibodies and Reagents;184
8.3.3.3; Analysis of Total Cellular Lysates;185
8.3.3.4; NF-B Activation Assay;185
8.3.3.5; Cell Death Assay;185
8.3.4;References;186
8.4;17 Unique Personalities Within the NF-B Family: Distinct Functions for p65 and RelB in the Osteoclast;188
8.4.1; Distinct Kinetics for Activation of p65 and RelB in the OC Lineage;189
8.4.2; Role of p65 in OC Apoptosis;189
8.4.3; Role of RelB in OC Differentiation;190
8.4.4; cRel Is Not Required for Osteoclastogenesis;190
8.4.5; Summary;191
8.4.6;References;192
9;Part V Roles of the TNF Family in Infectious Diseases and Interrelationship of the TNF Family and Pattern Recognition Receptor Signaling: Roles of the TNF Family in Infectious Diseases;193
9.1;18 Workshop Summary: Functions of the TNF Family in Infectious Disease;194
9.1.1; The Role of Soluble TNF, Membrane TNF, and Lymphotoxin in Mycobacterium tuberculosis Infection;194
9.1.2; Interplay Between Heme and TNF in Severe Malaria;195
9.1.3; TNF in Chagas Disease;195
9.1.4; Subversion of TNF-Mediated Viral Control by Poxviruses;195
9.1.5; 4-1BB/4-1BBL in Influenza and HIV Infections;196
9.1.6; A Lymphotoxin Pathway to Hepatocellular Carcinoma;196
9.1.7; Emerging Themes;197
9.1.8;References;197
9.2;19 Role of 4-1BBL and TRAF1 in the CD8 T Cell Response to Influenza Virus and HIV;199
9.2.1; Introduction;199
9.2.2; Role of TRAF1 in 4-1BB Signaling;199
9.2.3; How Unique Are 4-1BB-Induced Survival Signals?;201
9.2.4; Role of 4-1BBL and TRAF1 in Restoring Function in CD8 T Cells from Chronically HIV Infected Individuals;201
9.2.5; Role of 4-1BBL in Mild Versus Severe Influenza Virus Infection;202
9.2.6; Role of 4-1BBL and TRAF1 in T Cell Memory;203
9.2.7; A Model for the Maintenance of CD8 T Cell Memory;204
9.2.8; Concluding Remarks;205
9.2.9;References;205
9.3;20 Roles of Soluble and Membrane TNF and Related Ligands in Mycobacterial Infections: Effects of Selective and Non-selective TNF Inhibitors During Infection;209
9.3.1; Introduction;209
9.3.2; Roles of TNF in Mycobacterial Infections;210
9.3.3; Soluble TNF, Membrane-Bound TNF, and Lymphotoxins;210
9.3.4; Role of TNF in Experimental Animal Models of Tuberculosis Infection;212
9.3.5; Membrane TNF Protects from BCG and Acute Tuberculosis Infections;213
9.3.6; Lymphotoxins and LIGHT in Immunity to Mycobacterial Infections;214
9.3.7; Neutralization of TNF and Risks of New Infection and Reactivation of Latent Tuberculosis;214
9.3.8; Strategies to Block TNF Activities;215
9.3.9; TNF and Chemokines in Mycobacterial Infections;217
9.3.10; Conclusion;217
9.3.11;References;218
9.4;21 Poxviral TNFRs: Properties and Role in Viral Pathogenesis;224
9.4.1; Poxviruses;224
9.4.2; Poxviral TNF-Binding Proteins;224
9.4.3; vTNFRs in Pathogenesis;227
9.4.4; Ectromelia Virus;227
9.4.5; Conclusions;229
9.4.6;References;229
9.5;22 Heme Sensitization to TNF-Mediated Programmed Cell Death;232
9.5.1; Introduction;232
9.5.2; Malaria;233
9.5.3; A Central Role of Free Heme in the Pathogenesis of Severe Malaria;234
9.5.4; Free Heme Sensitizes Cells to Undergo TNF-Mediated Apoptosis;236
9.5.5; Concluding Remarks;237
9.5.6;References;238
9.6;23 TNF- and TNFR in Chagas Disease: From Protective Immunity to Pathogenesis of Chronic Cardiomyopathy;241
9.6.1; Introduction;241
9.6.2; TNF- Polymorphisms in Chagas Disease;242
9.6.3;TNF- in Trypanosoma cruzi Immunity;243
9.6.4;Beneficial Effects of TNF- Blockade in Trypanosoma cruzi Infection;244
9.6.5; Conclusions and Future Avenues;246
9.6.6;References;247
9.7;24 Lymphotoxins Link to Carcinogenesis: Friend or Foe? From Lymphoid Neogenesis to Hepatocellular Carcinoma and Prostate Cancer;251
9.7.1; Lymphotoxin: Past and Present;251
9.7.2; From Toxicity to Function;251
9.7.3; Lymphotoxin, Lymphoid Neogenesis, and Lymphoid Microarchitecture;252
9.7.4; Lymphotoxin and Inflammation;253
9.7.5; LTR Signaling in Health and Disease;255
9.7.6; NFB, Chronic Inflammation, and Cancer;255
9.7.7; Lymphotoxin and Its Link to Cancer;257
9.7.8; LTR Signaling in the Liver;258
9.7.9; Hepatic LTR Signaling and Hepatocellular Carcinoma;258
9.7.10;References;264
10;Part VI Roles of the TNF Family in Infectious Diseases and Interrelationship of the TNF Family and Pattern Recognition Receptor Signaling: Interrelationship of the TNF Family and Pattern Recognition Receptor Signaling;270
10.1;25 Anti-inflammatory Functions of Caspase-8;271
10.1.1; Involvement of Signaling Proteins Activated by TNF/NGF Family Members in Signaling Pathways Activated by Other Inducers;271
10.1.2; Inflammatory Processes Triggered by Caspase-8 Deficiency;272
10.1.3; Exploring the Mechanism for a Skin Inflammatory Disease Prompted by Caspase-8 Deficiency in the Epidermis Revealed an Inhibitory Effect of Caspase-8 on Signaling for IRF3 Activation;274
10.1.4; Regulation of RIG-I Signaling by Caspase-8;277
10.1.5; Epilogue;277
10.1.6;References;278
10.2;26 Endogenous Ligand-Induced Activation of TLR4 in Pre-metastatic Phase Is Both Downstream and Upstream of TNF Signaling;279
10.2.1; Discovery of Endogenous Ligands for TLR4 in Pre-metastatic Milieu;279
10.2.2; The Complex Paracrine Modes in TNFR and TLR4 Crosstalks;281
10.2.3; Conclusion;283
10.2.4;References;284
11;Part VII Novel Aspects of Immune Regulation by the TNF Family;287
11.1;27 Introductory Words About TL1A/DR3;288
11.1.1;References;290
11.2;28 Introductory Words About TWEAK/Fn14;292
11.2.1;References;294
11.3;29 Insights into TL1A and IBD Pathogenesis;295
11.3.1; Introduction;295
11.3.2;TL1A (TNFSF15) Is an IBD Severity Associated Gene ;296
11.3.3; Upstream Regulators of the TL1A-DR3 Signaling Pathway;297
11.3.4; Downstream Effects of the TL1A-DR3 Signaling Pathway;300
11.3.5; Role of TL1A in Inflammatory Diseases;301
11.3.6; Conclusion;302
11.3.7;References;302
11.4;30 The Role of TNFRSF25:TNFSF15 in Disease and Health?;305
11.4.1; Introduction;305
11.4.2; Structure, Expression and Signaling;306
11.4.3; TL1A:TNFR25 in T Cell Function;308
11.4.4; TL1A:TNFR25 in Auto-aggressive Disease;309
11.4.5; TL1A:TNFR25 in Health?;311
11.4.6;References;311
11.5;31 Identification of New Candidates as Mucosal Vaccine Adjuvant in TNF Family Cytokines;315
11.5.1; Mucosal Immunity and Vaccine;315
11.5.2; Identification of New Candidate Mucosal Vaccine Adjuvants Among TNF Superfamily Cytokines;316
11.5.3; Concluding Remarks;319
11.5.4;References;320
11.6;32 The TWEAK/Fn14 Pathway in Tissue Remodeling: For Better or for Worse;321
11.6.1; Introduction;321
11.6.2; TWEAK;323
11.6.3; Fn14;323
11.6.4; Fn14 Signaling;324
11.6.5; Role of TWEAK/Fn14 Pathway in Disease;326
11.6.6; Role of TWEAK/Fn14 in Intestinal Inflammation and Injury;332
11.6.7; Summary and Perspective;335
11.6.8;References;336
11.7;33 TWEAK and the Kidney: the Dual Role of a Multifunctional Cytokine;339
11.7.1; Introduction;339
11.7.2; TWEAK and Fn14 Expression in Renal Cells;340
11.7.3; TWEAK Biological Activity in the Kidney;341
11.7.3.1; Pro-inflammatory Effect of TWEAK in the Kidney;341
11.7.3.2; TWEAK and Renal Cell Death;341
11.7.3.3; TWEAK and Renal Cell Proliferation;342
11.7.4; TWEAK and Fn14 in Experimental Kidney Disease;343
11.7.4.1; Acute Kidney Injury;343
11.7.4.2; Non-inflammatory Renal Regeneration Model: Uninephrectomy;345
11.7.4.3; Autoimmune Kidney Disease: Lupus Nephritis;346
11.7.5; Future Lines of Research;346
11.7.6;References;347
11.8;34 TWEAK and TNF Regulation of Sclerostin: A Novel Pathway for the Regulation of Bone Remodelling;352
11.8.1; Introduction;352
11.8.2; TWEAK;352
11.8.3; A Role for TNF Family Members in Bone Remodeling;353
11.8.4; Human Osteoblasts and Osteoblast-Like Cell Lines Express Fn14 and TWEAK;353
11.8.5; TWEAK Inhibits In Vitro Mineralisation and Antagonizes the Osteogenic Effect of TNF;353
11.8.6; Effect of TWEAK and TNF on Osteoblast Proliferation;354
11.8.7; Effect of TWEAK and TNF on Osteoblast Osteogenic Gene Transcription;355
11.8.8; Interaction Between TWEAK and TNF;357
11.8.9; The Wnt Signalling Pathway and Inhibitors: Sclerostin;357
11.8.10; TWEAK Alone and in Combination with TNF Induce Sclerostin Expression;357
11.8.11; Concluding Remarks;358
11.8.12;References;360
12;Part VIII Control of Lymphocyte Function and Repertoire by the TNF Family;364
12.1;35 Workshop Summary: Control of Lymphocyte Function and Repertoire by the TNF Superfamily;365
12.2;36 The Canonical and Unconventional Ligands of the Herpesvirus Entry Mediator;367
12.2.1; Introduction;367
12.2.2; Canonical Ligands: LIGHT and LT;369
12.2.3; Unconventional Ligands: BTLA and CD160;370
12.2.4; Distinct Ligand Binding Sites on HVEM;371
12.2.5; Viral Ligands of HVEM and BTLA: HSV gD and UL144;371
12.2.6; The Trans and Cis of HVEM Signaling;372
12.2.7;References;373
12.3;37 The Lymphotoxin Pathway as a Novel Regulator of Dendritic Cell Function;377
12.3.1;References;384
12.4;38 Involvement of the Cytokine Receptor CD137 in Murine Hematopoiesis;389
12.4.1; Introduction;389
12.4.2; Effects of CD137 on Murine Hematopoietic Progenitor Cells;390
12.4.2.1; CD137 and Its Ligand Are Expressed in the Bone Marrow;390
12.4.2.2; CD137 Induces Proliferation and Colony Formation of Hematopoietic Progenitor Cells;390
12.4.2.3; CD137 Induces Cell Differentiation Toward Macrophages;392
12.4.3; Other Activities of CD137 in Hematopoiesis;393
12.4.4; Conclusion;394
12.4.5;References;395
12.5;39 LTBR-Pathway in Sjogrens Syndrome: CXCL13 Levels and B-cell-Enriched Ectopic Lymphoid Aggregates in NOD Mouse Lacrimal Glands Are Dependent on LTBR;397
12.5.1; The TNF Family and Inflammatory Versus Homeostatic Pathways;397
12.5.2; Ectopic Lymphoid Tissue Development and Homeostasis in Disease;397
12.5.3; What Is the Role of Ectopic Follicles in Disease;398
12.5.4; Clinical Utility of Dispersing Ectopic Follicles in Sjogrens Syndrome;398
12.5.5; Role of LTBR in Lymphocytic Infiltrates in Lacrimal Glands;399
12.5.6; Involvement of the LTBR Axis in Lacrimal Gland Pathology;400
12.5.7; Affymetrix Chip Analysis Implication of LTBR Pathway and Chemokine CXCL13;400
12.5.8; CXCL13 Production in Lacrimal Glands Lacking FDC Networks;402
12.5.9;References;403
12.6;40 MEK Kinase 1: Kinase Domain Deficiency in Mice Reveals a Role in Orchestrating the Thymus-Dependent Immunity and TNFR Family Signaling;405
12.6.1; Introduction;405
12.6.2; Activation of E3 Ub Ligase Itch by the T-Cell Receptor;406
12.6.3; Thymus-Dependent Immune Responses and TNFR Signaling in B Cells;407
12.6.4; Two-Stage Cytokine Receptor Signaling;408
12.6.5; Perspectives;409
12.6.6;References;410
13;Part IX Advances in Applying Our Knowledge to Therapy: Mechanisms of Pathological and Therapeutic Effects of the TNF Family ;412
13.1;41 Introduction to the Session Mechanisms of Pathological and Therapeutic Effects of the TNF Family;413
13.2;42 Mechanisms Regulating TNF-Driven Gut and Joint Inflammation;415
13.2.1; The Gut Joint Axis in Spondyloarthritis;415
13.2.2; Modeling Spondyloarthritis in Mice: Which Cells Are Targets of Pathogenic TNF?;416
13.2.3; NKT Cells: Regulators or Effectors in Arthritic Disease?;417
13.2.4;References;419
13.3;43 Lessons from Anti-TNF Biologics: Infliximab Failure in a TRAPS Family with the T50M Mutation in TNFRSF1A;421
13.3.1; Assessment of the Effect of Anti-TNF Biologicals in an Irish Family with the T50M Variant of TNFRSF1A;422
13.3.2; Therapeutic Options in the Treatment of TRAPS: A Revised View;425
13.3.3; Conclusion;428
13.3.4;References;429
13.4;44 Modalities of Experimental TNF Blockade In Vivo: Mouse Models;432
13.4.1; Introduction;432
13.4.2; Results and Discussion;433
13.4.2.1; Novel Humanized Mice for Studying TNF Inhibition In Vivo;433
13.4.2.2; Mouse Models to Evaluate Functions of TNF Produced by Distinct Cell Types or in Distinct Molecular Forms (or Both);436
13.4.2.3; Distinct Functions of TNF Produced by Individual Types of Immunocytes in Disease;436
13.4.2.4; Effects of Non-conventional TNF Blockers on Acute Septic Shock and on the Structure of Secondary Lymphoid Organs;439
13.4.3;References;440
13.5;45 Tumor Necrosis Factor- Signaling via TNFR1/p55 Is Deleterious Whereas TNFR2/p75 Signaling Is Protective in Adult Infarct Myocardium;443
13.5.1; Background;443
13.5.1.1; Aging and Angiogenesis;443
13.5.1.2; TNF, TNF Receptors, and Angiogenesis;443
13.5.1.3; Aging, TNF Signaling, and Post-ischemic Recovery;444
13.5.2; Results;445
13.5.2.1; Constitutive Expression of p75 Is Decreased in Human PB EPCs from Donors of Increasing Age;445
13.5.2.2; Post-AMI Survival and Functional Myocardial Recovery Is Impaired in Old p75KO Mice;445
13.5.2.3; Cardiac Troponin I (cTnI) Expression Is Increased in Infarct Border Zone in p75KO Mice;448
13.5.2.4; Capillary Density Is Decreased in Infarct and Infarct Border Zone in Old WT and Young and Old p75KO Mice;449
13.5.2.5; Compared to Old WT Mice Post-AMI Functional Capillary Density Is Decreased in Old p75KOs in Infarct Border Zone;449
13.5.2.6; Ischemia-Induced Apoptosis Is Increased in the Myocardium of Old p75KO Mice 28 Days Post-AMI;451
13.5.2.7; Expression of Several Angiogenic Growth and Stem Cell-Derived Factors and Their Receptors Is Decreased in Peripheral Blood EPCs from Adult Donors;451
13.5.3; Summary;454
13.5.4;References;456
13.6;46 TNF- Regulation of CD38 Expression in Human Airway Smooth Muscle: Role of MAP Kinases and NF-B;459
13.6.1; Introduction;459
13.6.2; CD38/cADPR Signaling Pathway;459
13.6.3; Regulation of CD38 Expression in ASM Cells;461
13.6.3.1; Cd38 Gene and Promoter;461
13.6.3.2; Cytokine Regulation of CD38 Expression;463
13.6.4; TNF- and CD38 Expression;463
13.6.4.1; TNF-;463
13.6.4.2; TNF- Signaling and MAP Kinases;464
13.6.5; Concluding Remarks;466
13.6.6;References;466
13.7;47 Functional Consequences of Disease-Associated Mutations in TNFR1 Elucidated by Transcriptome Analysis;470
13.7.1; Introduction;470
13.7.2; TNFR1 Mutations and TRAPS;471
13.7.3; Clinical Features;472
13.7.4; Dissecting the Molecular Pathogenesis of TRAPS;472
13.7.5; Altered Gene Expression Profile in Cells Expressing TNFR1 TRAPS Mutants;474
13.7.6;References;476
13.8;48 Tumor Necrosis Factor- and Kidney Function: Experimental Findings in Mice;480
13.8.1;Direct Effects of TNF- on Renal Hemodynamics and Excretory Function ;481
13.8.2;What Would Be the Mechanism (s) of These Renal Actions TNF-?;481
13.8.3;What Would Be the Mechanism of Natriuresis Induced by TNF- ? ;483
13.8.4; Renal mRNA Expression of Oxidative and Nitrosative Enzymes in Response to TNF Infusion;485
13.8.5; Conclusion;486
13.8.6;References;487
13.9;49 Strategies to Inhibit the Toxicity of Systemic TNF Treatment;490
13.9.1; Introduction;490
13.9.2; Inhibition of Matrix Metalloproteinases;491
13.9.3; Induction of HSP70;491
13.9.4; Inhibition of Cytokines;492
13.9.5; Conclusion;492
13.9.6;References;492
14;Part X Advances in Applying our Knowledge to Therapy: Rational Design of New Means for Therapeutic Modulation of Function of the TNF Family;494
14.1;50 Workshop Summary: Introduction to Rational Design of New Means for Therapeutic Modulation of Function of the TNF Family;495
14.1.1;References;498
14.2;51 Anti-inflammatory Effects of a Novel TNFR1-Selective Antagonistic TNF Mutant on Established Murine Collagen-Induced Arthritis;500
14.2.1; Anti-TNF Therapy for Autoimmune Diseases;500
14.2.2; Creating Functional Mutants with Advanced Medical Applications;501
14.2.3; Bioconjugation as a Polymeric DDS;503
14.2.4; Conclusion Remarks;505
14.2.5;References;505
14.3;52 A Proliferation-Inducing Ligand (APRIL): The Development of Antagonistic Agents as Potential Therapeutics and Deciphering the Role of Heparan Sulphate Proteoglycans (HSPGs) in APRIL Signalling;508
14.3.1; Introduction;508
14.3.2; The Development and Characterisation of Antagonistic Monoclonal Antibodies Against Human APRIL;509
14.3.3; The Role of HSPGs in APRIL Signalling;510
14.4;References;512
14.5;53 Genetic Engineering of Death Ligands for Improvement of Therapeutic Activity;514
14.5.1; Introduction;514
14.5.2; Stabilization of Trimer Formation;516
14.5.3; Conversion of Inactive Death Ligands into Highly Active Molecules Through Tumor-Directed Targeting;517
14.5.4; Targeting-Dependent Enhancement of TRAILs Antitumoral Activity;518
14.5.5; Exploiting Therapeutic Potential of CD95L- and TNF-Based Reagents: Targeted Activation and Prodrugs;520
14.5.6; Bifunctional Death Ligand Fusion Proteins;523
14.5.7; Conclusion;524
14.5.8;References;525
14.6;54 Computational Design of TNF Ligand-Based Protein Therapeutics;527
14.6.1; Concluding Remarks;535
14.6.2;References;536
15;Part XI Roles of the TNF Family in Neuronal Development, Function, and Pathology;541
15.1;55 Workshop Summary: Roles of the TNF Family in Neuronal Development, Function and Pathology;542
15.2;56 TNF: A Key Neuroinflammatory Mediator of Neurotoxicity and Neurodegeneration in Models of Parkinson's Disease;544
15.2.1;References;545
15.3;57 The Contribution of TNF to Synaptic Plasticity and Nervous System Function;546
15.3.1;References;558
15.4;58 Intracellular and Intercellular Cross Talk Between NGF and TNF;563
15.4.1; Introduction;563
15.4.2;TNF Signalling Through TNFR2 Modulates NGF Signalling ;563
15.4.3;NGF Appears to Change the Effects of Endogenous TNF on Neuronal Survival;564
15.4.4;Possible Contributions of Endogenous TNF to Tumourigenesis of Neuroblastomas ;565
15.4.5; Where Is the Endogenous Source of NGF in the Adult Nervous System?;565
15.4.6;A Possible Intercellular Loop of NGF and TNF Expression ;566
15.4.7; Conclusion;566
15.4.8;References;567
15.5;59 TNFR2 Target for Therapeutics Against Neurodegenerative Diseases?;570
15.5.1; TNF and Its Receptors;570
15.5.2; TNF and TNFRs in Neurodegenerative Disease;570
15.5.3; TNF and SK Channels;573
15.5.4; Statins and the TNFR2 Neuroprotective Pathway;574
15.5.5; Overall Discussion and Conclusion with Future Perspectives;575
15.5.6;References;575
15.6;60 A Role for Neuronal NF-B in Suppressing Neuroinflammation and Promoting Neuroprotection in the CNS;577
15.6.1; Introduction;577
15.6.2; Transcription Factor NF-B in EAE Pathology;577
15.6.3; Conditional Gene Targeting of IKK Kinase During Autoimmune, Demyelinating Disease;578
15.6.4; Proinflammatory and Neuroprotective Effects During EAE in nIKKKO Mice;580
15.6.5; Conclusion;582
15.6.6;References;582
16;Part XII Cell Death Mechanisms Controlled by the TNF Family;584
16.1;61 Workshop Summary: Cell Death Mechanisms Controlled by the TNF Family;585
16.1.1; Introduction;585
16.2;62 A RNA Interference Screen Identifies RIP3 as an Essential Inducer of TNF-Induced Programmed Necrosis;589
16.2.1; Introduction;589
16.2.2; Identification of RIP Kinases as Critical Mediators for Programmed Necrosis;589
16.2.3; RIP3 Is Recruited to the Cytoplasmic Signaling Complex and Interacts with RIP1 via the RHIM;590
16.2.4; The RHIM and Kinase Domains of RIP1 and RIP3 Are Essential for Programmed Necrosis;590
16.2.5; RIP3 Controls ROS Production;591
16.2.6; The Role of RIP3 in T-Cell Death;591
16.2.7; RIP3 Participates in Anti-viral Innate Immune Responses;592
16.2.8;References;593
16.3;63 The Extracellular Matrix Protein CCN1 Dictates TNF and FasL Cytotoxicity In Vivo;594
16.3.1; Introduction;594
16.3.2; The CCN Family of Extracellular Matrix Proteins;594
16.3.3; CCN Proteins and TNF Cytokines Synergize to Induce Apoptosis In Vitro and In Vivo;595
16.3.4; ROS Mediates Signaling Cross Talk Between CCNs and TNF or FasL;598
16.3.5; Future Prospects;599
16.3.6;References;599
16.4;64 Compartmentalization of TNF-Receptor 1 Signaling: TNF-R1-Associated Caspase-8 Mediates Activation of Acid Sphingomyelinase in Late Endosomes;603
16.4.1; TNF-Receptor Signaling;603
16.4.2; Non-apoptotic Signaling of TNF-Receptor 1;603
16.4.3; Apoptosis-Inducing Signals from TNF-Receptor 1;604
16.4.4; Mechanisms of Receptor Internalization;604
16.4.5; DISC Assembly Occurs on Internalized TNF-Receptosomes;605
16.4.6; A-SMase Activation by TNF;608
16.4.7; Caspase-8 Deficiency Prevents TNF Activation of A-SMase and Cathepsin D;609
16.4.8; Active Caspase-8 Colocalizes with Internalized TNF-Receptosomes and A-SMase;609
16.4.9; Proteolytic Cleavage of Pro-A-SMase Correlates with Enhanced Enzymatic Activity;610
16.4.10;References;611
16.5;65 TNF/TNF Receptor 1-Mediated Apoptosis in Hepatocytes;615
16.5.1; Introduction;615
16.5.2; The Biology of TNF and TNF Receptor 1 System in the Liver;616
16.5.3; The Signaling and Function of TNF Receptor 1 in the Liver;617
16.5.4; Other Unique Observations on TNFR1 in Hepatocytes;619
16.5.5;References;620
16.6;66 Regulation of Cell Death by c-FLIP Phosphorylation;623
16.6.1; Introduction;623
16.6.2; Activation of Apoptosis by Death Receptors;623
16.6.3; c-FLIP as a Regulator of the Cell Fate;624
16.6.4; Regulation of c-FLIP by Post-Translational Modifications;625
16.6.5; PKC-Mediated Phosphorylation Regulates the Stability of the Short c-FLIP Isoforms;626
16.6.6; Pursuing Interest on c-FLIP Ubiquitylation;627
16.6.7;References;627
17;Appendix I: Contributors to Abstracts of Talks and Posters at the 12th TNF Conference;629
18;Appendix II: Abstracts of Talks and Posters Presented at the 12th TNF Conference;640
18.1; KEYNOTE LECTURE;640
18.1.1; ORCHESTRATION OF THE TNF RESPONSE BY MESSENGER RNA STABILITY AND MICRORNAS;640
18.2; LECTURES ROLES OF THE TNF FAMILY IN TISSUE HOMEOSTASIS AND NORMAL DEVELOPMENT;641
18.2.1; BEYOND BONES - THE MULTIPLE FUNCTIONS OF RANKL-RANK;641
18.2.2; HAIR FOLLICLE RANK-LIGAND REGULATES EPITHELIAL GROWTH VIA BCL-3;641
18.2.3; TNFs IN HAIR AND MAMMARY GLAND DEVELOPMENT;642
18.2.4; TNF PRIMES ENDOTHELIAL CELLS FOR ANGIOGENIC SPROUTING BY INDUCING A TIP CELL PHENOTYPE;643
18.2.5; LTalpha CONTRIBUTES TO LYMPHATIC VESSEL DEVELOPMENT AND FUNCTION;643
18.2.6; TNF SIGNALING AND ITS PHYSIOLOGICAL ROLES IN DROSOPHILA;644
18.3; ROLES OF THE TNF FAMILY IN CANCER;644
18.3.1; THE EGFR PATHWAY: RECENT LESSONS IN SIGNAL TRANSDUCTION;644
18.3.2; STUDY OF APRIL EXPRESSION AND APRIL-MEDIATED SIGNALING IN BREAST CANCER;645
18.3.3; ROLE OF RECEPTOR ACTIVATOR OF NF-B LIGAND (RANKL) IN TUMORIGENESIS AND METASTASIS;646
18.3.4; TNF-MEDIATED MYELOID CELLS SURVIVAL IS NECESSARY FOR TUMOR GROWTH;648
18.3.5; FAS SIGNAL PROMOTES LUNG CANCER GROWTH BY RECRUITING MYELOID-DERIVED SUPPRESSOR CELLS VIA CANCER CELL-DERIVED PGE2;648
18.3.6; NF-KAPPAB INHIBITION AND SKIN CANCER: A VISCOUS CIRCLE OF CHRONIC INFLAMMATION AND IMMUNOSUPPRESSION DRIVEN BY TNFR1 IN KERTINOCYTES;649
18.3.7; ENDOGENOUS LIGAND-INDUCED ACTIVATION OF TLR4 IN PRE-METASTATIC PHASE IS BOTH DOWNSTREAM AND UPSTREAM OF TNF SIGNALING;650
18.3.8; MECHANISMS OF THE TUMOR-PROMOTING ACTION OF TNF- IN EPITHELIAL TUMORS;650
18.4; NOVEL ASPECTS OF SIGNALING ACTIVATION BY THE TNF FAMILY;651
18.4.1; NON-CANONICAL MODES OF UBIQUITINATION IN REGULATION OF TRANSCRIPTION: PROCESSING OF THE NF- B p105 AND ACTIVATION OF POLYCOMB REPRESSIVE COMPLEX 1;651
18.4.2; SIGNALING LESSONS FROM DEATH RECEPTORS;652
18.4.3; IN VIVO STUDY OF THE (PATHO)PHYSIOLOGICAL ROLE OF THE ANTI-APOPTOTIC AND ANTI-INFLAMMATORY PROTEIN A20, USING GENETICALLY MODIFIED MICE;653
18.4.4; REGULATION OF TNF-INDUCED JNK ACTIVATION AND INFLAMMATION BY SMOR1;654
18.4.5; CULLIN3-BASED POLYUBIQUITINATION AND P62-DEPENDENT AGGREGATION OF CASPASE-8 MEDIATE CELL EXTRINSIC APOPTOSIS SIGNALING;654
18.4.6; SELECTIVE BINDING OF LINEAR UBIQUITIN CHAINS TO NEMO (NF-B ESSENTIAL MODULATOR) IN NF-B ACTIVATION;655
18.4.7; A NOVEL UBIQUITIN LIGASE RECRUITED TO THE TNF-R1 SIGNALLING COMPLEX IS REQUIRED FOR EFFICIENT TNF-INDUCED NF-B ACTIVATION AND GENE INDUCTION;656
18.5; TRANSCRIPTIONAL NETWORKS AND SYSTEMS BIOLOGY;657
18.5.1; CHARACTERIZATION OF NOVEL TNF/NF-B SIGNALING PATHWAY COMPONENTS BY GENOME-WIDE RNAI;657
18.5.2; RNA-INTERFERENCE BASED SCREEN IDENTIFIES NEW FACTORS IMPORTANT FOR NF-kappaB ACTIVATION AND TERMINATION;657
18.5.3; CASEIN KINASE 1, NF-B, AND HUMAN LYMPHOMA CELL SURVIVAL;658
18.5.4; PATHOGENIC ROLE OF IL-6 WITH TNF- or IL-1 ON THE INDUCTION OF ACUTE PHASE PROTEINS IN CHRONIC INFLAMMATORY STATUS OF AUTOIMMUNE DISEASE;659
18.5.5; NEW INSIGHTS IN LTBR-MEDIATED NF-B ACTIVATION;659
18.5.6; THE NF-B SIGNALING SYSTEM AS AN INTEGRATOR OF DIVERSE SIGNALS;660
18.5.7; MATHEMATICAL MODELING OF THE TNF-a SIGNALING PATHWAY;660
18.5.8; DYNAMICS WITHIN THE CD95 DEATH-INDUCING SIGNALING COMPLEX DECIDE LIFE AND DEATH OF CELLS;661
18.5.9; TNF- SENSITIZES PRIMARY MOUSE HEPATOCYTES TO FAS/CD95-INDUCED APOPTOSIS: A SYSTEMS BIOLOGY APPROACH;662
18.5.10; UNIQUE PERSONALITIES WITHIN THE NF-B FAMILY: DISTINCT FUNCTIONS FOR P65 AND RELB IN THE OSTEOCLAST;662
18.5.11; THE INTERRELATIONSHIP BETWEEN NF-kappaB, Nrf2 AND KEAP1 IN CONTROLLING TNF INDUCED INFLAMMATORY RESPONSES;663
18.5.12; AATF IS A NOVEL ACTIVATOR OF THE C-JUN TRANSCRIPTION FACTOR UPON UV-LIGHT EXPOSURE;664
18.5.13; MICRORNA miR-146 IS A KEY REGULATOR OF AUTOIMMUNITY AND INFLAMMATION;665
18.5.14; MicroRNA-146a PROTECTS FROM TNF-INDUCED APOPTOSIS;666
18.5.15; miRNA REGULATION OF ENDOTHELIAL CELL RESPONSES TO TNF;666
18.6; ROLES OF THE TNF FAMILY IN INFECTIOUS DISEASES AND INTERRELATIONSHIP OF THE TNF FAMILY AND PATTERN RECOGNITION RECEPTOR SIGNALING;667
18.6.1; THE IL-1 RECEPTOR / TOLL-LIKE RECEPTOR SUPERFAMILY: 10 YEARS OF PROGRESS;667
18.6.2; ACTIVATION OF INNATE IMMUNE REACTION BY MAMMALIAN DNA THAT ESCAPED FROM DEGRADATION, LEADING TO ANEMIA AND ARTHRITIS;668
18.6.3; MALARIAL HEMOZOIN IS A Nalp3 INFLAMMASOME ACTIVATING DANGER SIGNAL;669
18.6.4; CASPASE-8 REGULATES CELLULAR RESPONSE TO PATTERN RECOGNITION RECEPTORS;669
18.6.5; CELL-AUTONOMOUS ROLE OF TNFR AND TLR SIGNALING PATHWAYS IN ANTI-BACTERIAL IMMUNITY;670
18.6.6; BEYOND TNFR SIGNALING: THE MULTIFUNCTIONALITY OF TRADD;671
18.6.7; THE FUNCTION OF TRADD IN SIGNALING THROUGH TUMOR NECROSIS FACTOR RECEPTOR 1 AND TRIF-DEPENDENT TOLL-LIKE RECEPTORS;672
18.6.8; ROLE OF 4-1BB AND RELATED TNFR FAMILY MEMBERS IN CD8 T CELL RESPONSES TO VIRUSES;672
18.6.9; CRITICAL ROLE OF MEMBERS OF TNF OF MYCOBACTERIAL INFECTION REACTIVATION OF INFECTION BY TNF INHIBITORS;673
18.6.10; TUMOUR N ECROSI FACTOR ALPHA PRODUCED BY MACROPHAGES AND NEUTROPHILS IS REQUIRED FOR INITIAL PULMONARY PROTECTIVE INNATE IMMUNE RESPONSES BUT IS DISPENSABLE FOR PROTECTIVE IMMUNITY DURING PERSISTENT M. tuberculosis INFECTION;674
18.6.11; A CRITICAL ROLE OF THE POXVIRUS CrmD PROTEIN, A TNF AND CHEMOKINE BINDING PROTEIN, IN IMMUNE EVASION AND PATHOGENESIS;675
18.6.12; HEME SENSITIZATION TO TNF-MEDIATED PROGRAMMED CELL DEATH DICTATES THE OUTCOME OF PLASMODIUM INFECTION IN MICE;676
18.6.13; TNF/TNFR1 SIGNALING UP-REGULATES CCR5 EXPRESSION ON CD8+ T LYMPHOCYTES AND PROMOTES HEART TISSUE DAMAGE IN TRYPANOSOMA CRUZI INFECTION: BENEFICIAL EFFECTS OF TNF BLOCKADE;677
18.6.14; A LYMPHOTOXIN-DRIVEN PATHWAY TO HEPATOCELLULAR CARCINOMA;678
18.7; NOVEL ASPECTS OF IMMUNE REGULATION BY THE TNF FAMILY;678
18.7.1; TL1A (TNFSF15): A MASTER REGULATOR OF MUCOSAL INFLAMMATION;678
18.7.2; TL1A-DR3 INTERACTIONS IN T-CELL MEDIATED AUTOIMMUNITY;680
18.7.3; TNFR25/TL1A CONTROL CD4 REGULATORY CELLS, TH17/TH2 POLARIZATION AND NKT-IL-13 ACTIVITY IMPORTANT IN MUCOSAL AND SYSTEMIC IMMUNITY;681
18.7.4; IDENTIFICATION OF NEW CANDIDATES AS MUCOSAL VACCINE ADJUVANT IN TNF SUPERFAMILY CYTOKINES;682
18.7.5; ROLE OF TWEAK/Fn14 PATHWAY IN INTESTINAL INFLAMMATION AND TISSUE REPAIR;683
18.7.6; TWEAK INDUCES PROLIFERATION IN RENAL TUBULAR EPITHELIUM: A ROLE IN RENAL HYPERPLASIA;684
18.7.7; THE EFFECTS OF TWEAK AND TNF ON HUMAN OSTEOBLASTS: MAPK DEPENDENT INDUCTION OF SCLEROSTIN EXPRESSION;685
18.7.8; TWEAK REGULATES PROINFLAMMATORY TNF RECEPTOR-1 SIGNALING;686
18.7.9; Fn14: A COMMON STRUCTURAL FRAMEWORK FOR SPECIES SEQUENCE DIVERGENCE;686
18.8; CONTROL OF LYMPHOCYTE FUNCTION AND REPERTOIRE BY THE TNF FAMILY;687
18.8.1; UNCONVENTIONAL LIGAND ACTIVATION OF HVEM MEDIATES CELL SURVIVAL;687
18.8.2; LYMPHOTOXIN-0 RECEPTOR SIGNALING LICENSES DENDRITIC CELLS TO PRIME CD8+ T CELL RESPONSES;688
18.8.3; THE TNF-FAMILY RECEPTORS RANK AND CD40 COOPERATIVELY REGULATE CENTRAL TOLERANCE IN THYMUS;688
18.8.4; THE DUAL ROLE OF TNF ON T CELL ACTIVATION;689
18.8.5; THE ROLE OF CD40 T CELLS IN AUTOIMMUNE DIABETES: THE IDENTIFICATION OF AUTOAGGRESSIVE T CELLS AND A MECHANISM TO THWART PERIPHERAL TOLERANCE;690
18.8.6; APRIL RESTORES B CELL SURVIVAL AND LPS ANTIBODY RESPONSE IN BTK-DEFICIENT MICE;691
18.8.7; REGULATION OF HEMATOPOIESIS BY CD137;692
18.8.8; THE LTR-PATHWAY PROMOTES B-CELL ACCUMULATION LARGELY VIA CXCL-13 EXPRESSION IN ECTOPIC LYMPHOID AGGREGATES IN NOD MOUSE LACRIMAL GLANDS;692
18.8.9; DIFFERENTIAL REQUIREMENT OF LTBR DURING THE MATURATION OF LYMPH NODE ANLAGEN STROMA;693
18.8.10; ANALYSIS OF B LYMPHOCYTE TUMOR NECROSIS FAMILY MEMBER SIGNALLING UTILIZING MEKK1KD TRANSGENIC MICE;694
18.9; NOVEL ASPECTS OF THE FUNCTIONS OF THE TRAFS AND CIAPS;694
18.9.1; PROTEIN UBIQUITINATION CASCADES AND SIGNALING BY TNF AND TOLL RECEPTORS;694
18.9.2; A SIGNALING PATHWAY FROM TNF RECEPTOR TO CELL DEATH;695
18.9.3; CRYSTAL STRUCTURE OF TRAF6 REVEALS SPECIFICITY AND MECHANISM OF TRAF6-MEDIATED UBIQUITINATION;696
18.9.4; TRAF2 BALANCES THE LEVELS OF cIAP1 AND cIAP2 THEREBY PROTECTING CANCER CELLS FROM TNF INDUCED CELL DEATH;697
18.9.5; TUMOR NECROSIS FACTOR (TNF) RECEPTOR-ASSOCIATED FACTOR 1 (TRAF1) ENHANCES PROINFLAMMATORY TNF RECEPTOR-2 (TNFR2) SIGNALING AND MODIFIES TNFR1-TNFR2 COOPERATION;698
18.9.6; CELLULAR INHIBITORS OF APOPTOSIS (c-IAPs) ARE CRITICAL REGULATORS OF TNF FAMILY MEDIATED SIGNALING;699
18.9.7; THE cIAP1 AND cIAP2 INTERACTING DOMAIN OF TRAF2 IS IMPORTANT FOR TNF AND TWEAK INDUCED NF-B AND PROTECTION AGAINST TNF INDUCED APOPTOSIS;699
18.10; ADVANCES IN APPLYING OUR KNOWLEDGE TO THERAPY;700
18.10.1; AN UPDATE ON LESSONS LEARNED FROM ANTI-TNF THERAPY OF RHEUMATOID ARTHRITIS;700
18.10.2; BLOCKADE OF THE LYMPHOTOXIN-LIGHT PATHWAY AND THE TREATMENT OF AUTOIMMUNE DISEASE;701
18.10.3; EXPLORATION OF THE ROLES OF SOLUBLE AND TRANSMEMBRANE TNF IN ANIMAL MODELS OF INFLAMMATION AND IMMUNITY: COMPARATIVE STUDIES OF SELECTIVE INHIBITORS OF SOLUBLE TNF TO NONSELECTIVE ANTI-TNF BIOLOGICS;702
18.11; MECHANISMS OF PATHOLOGICAL THERAPEUTIC EFFECTSOF THE TNF FAMILY;703
18.11.1; TNF DRIVEN ACTIVATION OF INVARIANT NKT CELLS REGULATES COMBINED GUT AND JOINT INFLAMMATION;703
18.11.2; TNF PRIMING OF TYPE I IFN RESPONSES IN MONOCYTES AND MACROPHAGES;704
18.11.3; THE ANTI-TNF DRUG, INFLIXIMAB, HAS A PROINFLAMMATORY ACTION IN PATIENTS WITH TUMOR NECROSIS FACTOR RECEPTOR-ASSOCIATED PERIODIC SYNDROME (TRAPS);705
18.11.4;SCIENCE OF TNF BLOCKADE IN VIVO;706
18.11.5; TNF-INDUCIBLE INHIBITOR I-KAPPAB EPSILON MODULATES IL-2 EXPRESSION IN T CELLS THROUGH REGULATION OF C-REL: IMPLICATIONS FOR CHRONIC INFLAMMATORY DISEASE;707
18.11.6; TUMOR NECROSIS FACTOR-A P75 RECEPTOR IS REQUIRED IN POST-MI RECOVERY IN ADULT HEART;708
18.11.7; TNF-ALPHA REGULATION OF CD38 EXPRESSION IN HUMAN AIRWAY SMOOTH MUSCLE: ROLE OF MAP KINASES AND NF-KAPPA B.;709
18.11.8; FUNCTIONAL CONSEQUENCES OF DISEASE-ASSOCIATED MUTATIONS IN TNFR1 ELUCIDATED BY TRANSCRIPTOME ANALYSIS;710
18.11.9; THE ROLE OF TNF SIGNALING IN SPONTANEOUS COLITIS DEVELOPMENT IN MICE LACKING NEMO SPECIFICALLY IN INTESTINAL EPITHELIAL CELLS;711
18.11.10; EFFECTS OF TNF- ON RENAL HEMODYNAMICS AND EXCRETORY FUNCTION IN MICE;712
18.11.11; LIPOPOLYSACCHARIDE PLUS GALACTOSAMINE-INDUCED FATAL HEPATITIS MEDIATED BY SECRETED TNF REQUIRES CASPASE-8 AND THE TWO BH3-ONLY PROTEINS BID AND BIM;713
18.11.12; STRATEGIES TO INHIBIT THE TOXICITY OF SYSTEMIC TNF TREATMENT WITH RETENTION OF ITS ANTITUMOR EFFECT;714
18.12; RATIONAL DESIGN OF NEW MEANS FOR THERAPEUTIC MODULATION OF FUNCTION OF THE TNF FAMILY;715
18.12.1; THE STALK REGION OF THE TNF RECEPTORS HIGHLY DETERMINES SOLUBLE TNF RESPONSIVENESS;715
18.12.2; THE EFFECT OF THERAPEUTIC ANTI-TNF AGENTS ON REVERSE SIGNALING VIA MEMBRANE TNF;716
18.12.3; DETERMINANTS FOR PRODOMAIN INHIBITION OF THE TNF- CONVERTING ENZYME (TACE) ZYMOGEN STATE;716
18.12.4; CREATION OF MUTANT LYMPHOTOXIN-ALPHAS WITH ENHANCED BIOACTIVITIES BY PHAGE DISPLAY TECHNIQUE;717
18.12.5; PHARMACOLOGICAL INHIBITION OF Tpl2 KINASE BLOCKS TNFalpha PRODUCTION IN HUMAN MONOCYTES AND MAY REPRESENT A NOVEL TREATMENT FOR RHEUMATOID ARTHRITIS;718
18.12.6; THE DISCOVERY OF A SERIES OF NOVEL SMALL MOLECULE MACROCYCLIC TNF ANTAGONISTS;719
18.12.7; BIOLOGICAL ACTIVITY OF ECTODYSPLASIN A IS CONDITIONED BY ITS COLLAGEN AND HEPARAN SULFATE PROTEOGLYCAN-BINDING DOMAINS;719
18.12.8; NOVEL MECHANISM OF ACTION FOR ANTI-LYMPHOTOXIN-ALPHA IN AUTOIMMUNE DISEASE: DEPLETION OF TH1 AND TH17 CELLS;720
18.12.9; THE DEVELOPMENT AND CHARACTERIZATION OF APRIL ANTAGONISTIC AGENTS;720
18.12.10; Fn14-TRAIL, A CHIMERIC INTERCELLULAR SIGNAL EXCHANGER, ATTENUATES EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS;721
18.12.11; NOVEL TRAIL VARIANTS FOR TARGETED CANCER THERAPY;722
18.12.12; DESIGNED RECEPTOR SPECIFIC RHTRAIL VARIANTS ENHANCE INDUCTION OF APOPTOSIS IN CANCER CELLS;723
18.12.13; APOMAB, A FULLY HUMAN AGONISTIC DR5 MONOCLONAL ANTIBODY INHIBITS TUMOUR GROWTH AND OSTEOLYSIS IN MURINE MODELS OF BREAST CANCER DEVELOPMENT AND PROGRESSION;724
18.13; ROLES OF THE TNF FAMILY IN NEURONAL DEVELOPMENT, FUNCTION PATHOLOGY;725
18.13.1; CENTRAL AND SYSTEMIC ACTION OF CYTOKINES IN NEURODEGENERATION;725
18.13.2; In vivo AND in vitro VALIDATION OF TNF AS A KEY NEUROINFLAMMATORY MEDIATOR OF NEUROTOXICITY AND NEURODEGENERATION IN MODELS OF PARKINSON'S DISEASE;726
18.13.3; THE CONTRIBUTION OF TNF TO SYNAPTIC PLASTICITY AND NERVOUS SYSTEM FUNCTION;727
18.13.4; AXONAL SELF-DESTRUCTION AND NEURODEGENERATIVE DISEASE;727
18.13.5; TNFalpha CHANGES DOWNSTREAM PATHWAYS OF NGF SIGNALLING FROM Erk1/2 TO Akt, WHICH BLOCKS NGF-DEPENDENT DIFFERENTIATION OF NEUROBLASTOMA CELLS;728
18.13.6; TNF RECEPTOR 2 SIGNALING: A TARGET FOR THERAPEUTIC INTERVENTIONS AGAINST NEURODEGENERATIVE DISEASES?;729
18.13.7; CASPASE 8 MEDIATES NEURON DEATH FOLLOWING in vivo AND in vitro EXCITOTOXIC INJURY;729
18.13.8; THE DEATH RECEPTOR ANTAGONIST C-FLIP IS NECESSARY FOR NEURONAL DIFFERENTIATION MEDIATED BY NEUROTROPHINS;730
18.13.9; NEURONAL NF-B (IKK) SUPPRESSES NEUROINFLAMMATION AND PROTECTS AGAINST NEUROLOGICAL DEFICITS IN DEMYELINATING CNS DISEASE;731
18.14; CELL DEATH MECHANISMS CONTROLLED BY THE TNF FAMILY;732
18.14.1; PROGRAMMED, ACCIDENTAL AND SECONDARY NECROSIS CONVERGE ON SIMILAR CELLULAR DISINTEGRATION FEATURES;732
18.14.2; RIBOFLAVIN KINASE COUPLES TNF RECEPTOR 1 TO NADPH OXIDASE AND APOPTOSIS;733
18.14.3; ATIA, A MULTI-TASK PROTEIN THAT PROTECTS CELLS AGAINST TNF-INDUCED APOPTOSIS;733
18.14.4; A RNA INTERFERENCE SCREEN IDENTIFIES NOVEL REGULATORS OF TNF-INDUCED PROGRAMMED NECROSIS;734
18.14.5; COMPARTMENTALIZATION OF TNF-R1 SIGNALING: CASPASE-8 AND CASPASE-7 SEQUENTIALLY MEDIATE ACTIVATION OF ACID SPINGOMYELINASE IN INTERNALIZED TNF-R1 RECEPTOSOMES;735
18.14.6; TNF RECEPTOR-1 (P55) AND DISC COMPONENTS TRANSLOCATE TO THE MITOCHONDRIA AND NUCLEUS IN TNF-TREATED HEPATOCYTES;735
18.14.7; FAS LIGAND SECRETION AND SELF-TOLERANCE IS REGULATED BY THE WISKOTT-ALDRICH SYNDROME PROTEIN;736
18.14.8; TNFR1 HAS AN EARLY UBIQUITINATION-DEPENDENT, NF-B-INDEPENDENT CELL DEATH CHECKPOINT;737
18.14.9; TNFa AND Fasl CYTOTOXICITY IS REGULATED BY THE EXTRACELLULAR MATRIX PROTEIN CCN1 in vitro AND in vivo;738
18.14.10; NON-CANONICAL NF-B SIGNALING PATHWAY IS REQUIRED FOR TNFA AUTOCRINE AND NECROSIS IN L929 CELLS;739
18.14.11; THE FORM OF FAS LIGAND DETERMINES WHETHER RETINAL GANGLION CELLS SURVIVE OR DIE DURING GLAUCOMA;740
18.14.12; FATAL LYMPHOPROLIFERATIVE DISEASE IN FASL- AND TRAIL DOUBLE-DEFICIENT MICE DUE TO FAILURE OF MATURE LYMPHOCYTE ACTIVATION-INDUCED CELL DEATH;741
18.14.13; DcR2 PROTECTS CANCER CELLS FROM TRAIL-INDUCED APOPTOSIS BY ACTIVATING Akt;742
18.14.14; ANALYSIS OF KNOCKOUT/ KNOCKIN MICE THAT EXPRESS A MUTANT FasL LACKING THE INTRACELLULAR DOMAIN;742
18.14.15; XIAP LOSS CONVERTS FAS-INDUCED APOPTOSIS SIGNALING IN HEPATOCYTES FROM TYPE II INTO TYPE I;743
18.14.16; c- FLIP PROTEINS AT THE NEXUS POINT OF FATE-DETERMINING SIGNALS ;743
18.15; Posters ROLES OF THE TNF FAMILY IN TISSUE HOMEOSTASIS AND NORMAL DEVELOPMENT;744
18.15.1; CHEMOKINES AS TARGETS OF EDA - A ROLE IN HAIR FOLLICLE DEVELOPMENT?;744
18.15.2; CASPASE-8 DEFICIENCY IN EPIDERMAL KERATINOCYTES TRIGGERS AN INFLAMMATORY SKIN DISEASE;745
18.16; ROLES OF THE TNF FAMILY IN CANCER;746
18.16.1; SUPPRESSION OF TUMOR GROWTH AND INTERRUPTION OF TUMOR ANGIOGENESIS BY SELECTIVE INHIBITION OF EITHER TNFR1/P55 OR TNFR2/75 IN MURINE MODEL OF LUNG CARCINOMA;746
18.16.2; INHIBITION OF TNFa/NIK/NF-kB TRANSDUCTION PATHWAY AS A POSSIBLE TARGET FOR PROSTATE CANCER TREATMENT;748
18.16.3; ERK and P38 PROMOTE SURVIVAL IN VITRO BY TNF-ALPHA STIMULATION IN PROSTATE CANCER;749
18.16.4; FUNCTION AND SIGNALING OF TRAIL IN PRIMARY HUMAN LEUKEMIA CELLS;750
18.16.5; STUDIES ON THE MECHANISM OF ACTION AND RESISTANCE TO TNFALPHA IN SOFT TISSUE SARCOMAS;750
18.16.6; LEUKOCYTE-DERIVED TNF- PROMOTES TUMOR GROWTH IN A SPONTANEOUS MODEL OF MAMMARY CARCINOGENESIS;751
18.16.7; ROLE OF B CELL IN TWO-STAGE SKIN CARCINOGENESIS;752
18.16.8; CO-EXPRESSION OF CD40L AND CD70 BY MELANOMA CELLS STIMULATES ANTI-TUMOUR IMMUNE RESPONSE;753
18.17; NOVEL ASPECTS OF SIGNALING ACTIVATION BY THE TNF FAMILY;754
18.17.1; ESSENTIAL ROLE OF TNF-INDUCIBLE ZINC FINGER PROTEIN A20 ON THE DEATH RECEPTOR-MEDIATED APOPTOTIC CELL DEATH THROUGH THE BLUNTING JNK SIGNALLING;754
18.17.2; ADP-RIBOSYLATION OF HUMAN TNF-ALPHA BY ADP-RIBOSYLTRANSFERASE-1 (ART1);755
18.18; TRANSCRIPTIONAL NETWORKS AND SYSTEMS BIOLOGY;756
18.18.1; PKC- AKTS TOGETHER DURING TNF SIGNALLING;756
18.18.2; A PTP4A3 PEPTIDE PIMAP39 MODULATES TNF-alpha LEVELS AND ENDOTOXIC SHOCK;757
18.18.3; CROSS-TALK OF APOPTOSIS SIGNAL-REGULATING KINASE 1 (ASK1) AND HIF-1ALPHA PROTEIN AS ESSENTIAL PATHWAY FOR LIGAND-INDUCED TOLL-LIKE RECEPTOR 4-MEDIATED EXPRESSION OF PRO-INFLAMMATORY CYTOKINES;758
18.18.4; EXPRESSION OF TNFALPHA-ACTIVATED NFKAPPAB-DEPENDENT GENES IS AFFECTED BY HYPERTHERMIA AND ACTIVE HSF1;759
18.19; ROLES OF THE TNF FAMILY IN INFECTIOUS DISEASES AND INTERRELATIONSHIP OF THE TNF FAMILY AND PPR-SIGNALING;760
18.19.1; PHOSPHATASE PTP1B NEGATIVELY REGULATES MYD88- AND TRIF-DEPENDENT PROINFLAMMATORY CYTOKINE AND TYPE I INTERFERON PRODUCTION IN TLR-TRIGGERED MACROPHAGES;760
18.19.2; SHP-2 PHOSPHATASE DIFFERENTLY REGULATES MYD88- AND TRIF-DEPENDENT SIGNAL TRANSDUCTION IN LPS RESPONSE;761
18.19.3; CHARACTERISTICS AND FUNCTION OF ECTROMELIA GENE EVM008;761
18.19.4; IMPORTANCE OF TRAF1 SIGNALING DOWNSTREAM OF 4-1BB IN MEDIATING CD8 T CELL SURVIVAL;762
18.19.5; THE ROLE OF 4-1BBL IN RESCUING FUNCTIONALLY IMPAIRED HIV-SPECIFIC CD8 T CELLS;763
18.19.6; THE ROLE OF GITR IN CD8 T CELL RESPONSES TO INFLUENZA VIRUS;764
18.19.7; THE ROLE OF TRAF1 IN REGULATING TRAF2 STABILITY DOWNSTREAM OF 4-1BB SIGNALING;764
18.19.8; MOLECULAR CHARACTERIZATION OF CRMD, THE TNF AND CHEMOKINE DECOY RECEPTOR OF POXVIRUS;765
18.20; NOVEL ASPECTS OF IMMUNE REGULATION BY THE TNF FAMILY;766
18.20.1; STRUCTURAL AND FUNCTIONAL ANALYSIS OF DEATH RECEPTOR-6;766
18.20.2; CHARACTERIZATION OF DR6 SIGNALING. CELL SPECIFICITY IN APOPTOSIS INDUCTION AND NF- B ACTIVATION;767
18.20.3; ESSENTIAL ROLE OF TNFRSF25/TL1A IN THE DEVELOPMENT OF ALLERGIC LUNG INFLAMMATION AND INFLAMMATORY BOWEL DISEASE;768
18.20.4; APRIL (TNFSF13), A SIGNIFICANT IMMUNE MODULATOR IN A MODEL OF RHEUMATOID ARTHRITIS, IN ALLERGIC LUNG INFLAMMATION AND IN ORAL/MUCOSAL IMMUNITY;768
18.21; CONTROL OF LYMPHOCYTE FUNCTION AND REPERTOIRE BY THE TNF FAMILY;769
18.21.1; ROLES OF NIK IN THYMIC EPITHELIAL CELLS FOR THE ESTABLISHMENT OF CENTRAL TOLERANCE;769
18.21.2; LYMHOTOXIN-B-RECEPTOR SIGNALING IS REQUIRED TO LICENSE DC FOR CROSS-PRIMING;770
18.21.3; LYMPHOID TISSUE INDUCER CELLS CONTROL CD8A- DENDRITIC CELL HOMEOSTASIS VIA THE LYMPHOTOXIN-BETA RECEPTOR PATHWAY;771
18.21.4; ROLE OF TNFRI AS A COSTIMULATORY MOLECULE DURING THE EARLY PHASE OF TCR STIMULATION IN CD3 T LYMPHOCYTES;772
18.21.5; LYMPHOTOXIN RECEPTOR SIGNALING SUPPORTS A UNIQUE STROMAL CELL NICHE THAT SUPPORTS IGA CLASS SWITCH RECOMBINATION IN THE INTESTINAL LAMINA PROPRIA;773
18.21.6; FUNCTIONAL CHARACTERIZATION OF CHIMERICAL RECEPTORS RANK-TNFR2 AND ANALYSIS OF THEIR INTERACTION WITH ADAPTOR PROTEINS TRAF;774
18.21.7; TNF RECEPTOR ASSOCIATED FACTOR 1 (TRAF1) MODIFIES CRYSTALLINE SILICA INDUCED LUNG INJURY;774
18.21.8; TRAF1 REGULATES TWEAK AND LTAB2-INDUCED NFKB SIGNALLING;775
18.22; MECHANISMS OF PATHOLOGICAL THERAPEUTIC EFFECTS OF THE TNF FAMILY;776
18.22.1; TRAIL INDUCED CELL DEATH IN COLON CARCINOMA CELLS IN VIVO AND IN VITRO: SENSITISATION BY ONCOGENES AND BY OTHER THERAPEUTICS;776
18.22.2; RELATION OF PRO-INFLAMMATORY AND ANTI-INFLAMMATORY CYTOKINES WITH MEDIATORS OF BONE REMODELATING SYSTEM IN PSORIATIC ARTHRITIS;777
18.22.3; THE REGULATION OF THE AMOUNT OF EXTRA CELLULAR DNA FIBRES BY THE TNF SUPER FAMILY;778
18.22.4; INDUCTION OF PRIMARY SCLEROSING CHOLANGITIS-LIKE DISEASE BY DR5-MEDIATED APOPTOSIS;779
18.22.5; LUPUS SERUM INDUCES SKIN INFLAMMATION THROUGH TNFR1 SIGNALING PATHWAY;780
18.22.6; CD8 T CELL-MEDIATED IMMUNE RESPONSES AGAINST CROSS-PRESENTING LIVER SINUSOIDAL ENDOTHELIAL CELLS LEADS TO HEPATITIS;781
18.22.7; FUNCTIONAL CONSEQUENCES OF MUTATIONS IN TNFRSF1A, COMPARISON OF IN VITRO CELLULAR EVENTS TO FINDINGS FROM TISSUE SAMPLES ISOLATED FROM PATIENTS WITH TUMOUR NECROSIS FACTOR RECEPTOR-ASSOCIATED PERIODIC SYNDROME (TRAPS);782
18.22.8; SIGNALING PATHWAYS OF MUTANT TUMOUR NECROSIS FACTOR RECEPTOR 1(TNFR1);783
18.22.9; EFFECT OF INFLIXIMAB TREATMENT ON CIRCULATING MONOCYTES IN RHEUMATOID ARTHRITIS PATIENTS: DIFFERENCES BETWEEN EARLY AND LATE DISEASE;783
18.22.10; APRIL EXPRESSION AND TARGETTING IN AUTOIMMUNE DISEASES;784
18.22.11; TNF SHEDDING AND EPIDERMAL INFLAMMATION IS CONTROLLED BY JUN/AP-1;785
18.22.12; DISTINCT CONTRIBUTIONS OF T CELL-DERIVED AND MACROPHAGE-DERIVED TNF IN PATHOGENESIS OF COLLAGEN INDUCED ARTHRITIS AND EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS;786
18.22.13; HSP70 DEPENDENT ZINC PROTECTION AGAINST TNF-INDUCED LETHAL INFLAMMATION ALLOWS FOR A SAFER ANTITUMOR THERAPY;787
18.22.14; RESISTANCE OF SPRET/EI MICE TO TNF-INDUCED LETHAL SHOCK;787
18.22.15; ABLATION OF c-FLIP AUGMENTS CD95- AND GALACTOSAMINE/LPS-INDUCED LIVER INJURY THROUGH ACTIVATION OF c-JUN N-TERMINAL KINASE (JNK);788
18.23; RATIONAL DESIGN OF NEW MEANS FOR THERAPEUTIC MODULATION OF FUNCTION OF THE TNF;789
18.23.1; MODULATORY EFFECT OF SILIBININ ON THE CYTOKINE PRODUCTION AND FUNGICIDAL ACTIVITY OF HUMAN MONOCYTES INFECTED IN VITRO WITH PARACOCCIDIOIDES BRASILIENSIS;789
18.23.2; APOPTOSIS-INDUCING ACTIVITY OF SOLUBLE TRAIL EXPRESSED IN MESENCHYMAL STEM CELLS ON HUMAN CANCER CELLS;790
18.23.3; ANALYSIS OF LIGAND RECEPTOR INTERACTION WITH NEW SINGLE CHAIN TNF DERIVATIVES;791
18.23.4; DOMINANT NEGATIVE TNF PROTECTS FROM MYCOBACTERIUM BOVIS BCG AND ENDOTOXIN-INDUCED LIVER INJURY WITHOUT COMPROMISING HOST IMMUNITY TO MYCOBACTERIUM TUBERCULOSIS AND BCG INFECTIONS;792
18.23.5; THE TUMOR NECROSIS FACTOR-A CONVERTING ENZYME (TACE) IS REGULATED BY PHYSIOLOGICAL IONIC STRENGTH;793
18.23.6; ENHANCED ANTI-TUMOR EFFICACY OF A DR5-SPECIFIC TRAIL VARIANT OVER RHTRAIL IN A BIOLUMINESCENT OVARIAN CANCER XENOGRAFT MODEL;793
18.23.7; TARGET CELL-RESTRICTED STIMULATION OF THE CD95 (APO-1/FAS) DEATH RECEPTOR WITH VARIOUS BISPECIFIC CD20XCD95 ANTIBODIES;794
18.23.8; SENSITIZATION OF PROSTATE CANCER CELLS TO TRAIL-MEDIATED APOPTOSIS BY THE TUMOR-SUPPRESSING MATAIRESINOL LIGNAN;795
18.23.9; RECEPTOR ACTIVATION BY SOLUBLE OX40 LIGAND AND 41BB LIGAND IS ENHANCED BY OLIGOMERIZATION AND CELL SURFACE IMMOBILIZATION;796
18.23.10; RELEVANCE OF OLIGOMERIZATION AND CELL SURFACE IMMOBILIZATION FOR THE ACTIVITY OF SOLUBLE VARIANTS OF CD27L AND GITRL;797
18.23.11; TRAIL FUSED TO SURFACTANT PROTEIN-D AND COLLECTIN-11 AS MODEL FOR TNF-SF COLLECTIN FUSION PROTEINS;797
18.23.12; MUTANT TNF ELICITS MUCOSAL AND SYSTEMIC IMMUNITY AGAINST HIV-1 AND INFLUENZA VIRUS;798
18.23.13; DEVELOPMENT OF A NOVEL METHOD USING PHAGE DISPLAY, GENE SHUFFLING AND IMPROVED RECEPTOR SELECTIVITY TO PRODUCE MUTANT TNFS;799
18.23.14; ANTI-INFLAMMATORY EFFECTS OF A NOVEL TNFR1-SELECTIVE ANTAGONISTIC TNF MUTANT ON ESTABLISHED MURINE COLLAGEN-INDUCED ARTHRITIS;800
18.23.15; RECEPTOR INTERACTION OF TUMOR NECROSIS FACTOR (TNF) BASED ON 3D STRUCTURAL ANALYSIS OF A FULLY ACTIVE TNFR1-SELECTIVE TNF MUTANT;801
18.23.16; THE DEVELOPMENT OF FULLY ACTIVE RECEPTOR-SELECTIVE TUMOR NECROSIS FACTOR (TNF) MUTANTS;802
18.23.17; THE ROLE OF HEPARAN SULFATE PROTEOGYCANS IN APRIL SIGNALLING;803
18.23.18; ENHANCEMENT OF ANTITUMOR PROPERTIES OF RHTRAIL BY AFFINITY INCREASE TOWARD ITS DEATH RECEPTORS;804
18.23.19; IMPROVED TUMOR CELL KILLING BY TRAIL REQUIRES SELECTIVE AND HIGH AFFINITY RECEPTOR ACTIVATION;805
18.23.20; COMPUTATIONAL DESIGN OF RECEPTOR SELECTIVE TRAIL VARIANTS;806
18.23.21; EFFICACY OF ANTI-TNF-A ANTIBODIES IN INTESTINAL CELL LINES SYSTEM;807
18.24; ROLES OF THE TNF FAMILY IN NEURONAL DEVELOPMENT, FUNCTION PATHOLOGY;808
18.24.1; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND-RELATED SIGNAL TRANSDUCTION IN NEURODEGENERATIVE PROCESSES;808
18.24.2; APOPTOSIS REGULATION IN NEUROSECRETORY CELLS OF HYPOTHALAMUS OF AGED TNF-KNOCKOUT MICE;809
18.25; CELL DEATH MECHANISMS CONTROLLED BY THE TNF FAMILY;809
18.25.1; ASSOCIATION OF FASL AND CAVEOLIN-1 IN LIPID RAFTS IS ESSENTIAL FOR THE ONSET OF FASL-MEDIATED CELL DEATH;809
18.25.2; TNF ALPHA INDUCE SHEDDING OF CD30 AND CD45 AND LDH RELEASE FROM K-562 CELLS;810
18.25.3; DIFFERENTIAL ROLE OF FLIP ISOFORMS IN TNF-INDUCED CELL LIFE AND DEATH RESPONSES;811
18.25.4; DEATH WITHOUT LIGANDS: NOVEL APPROACH IN INDUCTION OF TNF RECEPTOR SUPERFAMILY MEDIATED CELL DEATH;811
18.25.5; INVOLVEMENT OF ENDOCYTOSIS IN TRAIL-R1/DR4 AND TRAIL-R2/DR5 TRAFFICKING AND SIGNALING;812
18.25.6; GENERATION OF LMP1-TR1/2 FUSION PROTEINS AND RECOMBINANT TRAIL;813
18.25.7; ENHANCED CASPASE-8 ACTIVATION WITHIN THE DISC PRIMES OVER THE MITOCHONDRIAL PATHWAY TO SENSITIZE DCR2 EXPRESSING CELLS TO TRAIL INDUCED CELL DEATH AFTER CHEMOTHERAPY;814
18.25.8; INHIBITION OF CASPASES ENHANCES THE CYTOTOXIC EFFECT OF TNF IN HUMAN MYELOMONOCYTIC U937 CELL LINE;814
18.25.9; ANCHORAGE DEPENDENCY OF TNF AND CD40 LIGAND-INDUCED MAPK SIGNALLING;815
18.25.10; LIFEGUARD DIRECTLY INTERACTS WITH NEUROBLASTOMA-DERIVED SULFHYDRYL OXIDASE;816
18.25.11; MEMBRANE FAS LIGAND CLEARS BACTERIA AND SOLUBLE FAS LIGAND PROTECTS HOST TISSUE DURING S. AUREUS INDUCED ENDOPHTHALMITIS;817
18.25.12; TRAIL RESISTANCE IN NON-TRANSFORMED CELLS IS PROVIDED BY MULTIPLE FACTORS;818
18.25.13; DOWNREGULATION OF C-FLIP PROMOTES CASPASE-DEPENDENT JNK ACTIVATION AND REACTIVE OXYGEN SPECIES ACCUMULATION IN TUMOR CELLS;819
18.25.14; SEVERAL MECHANISMS FOR THE REGULATION OF HUMAN T CELL BLAST ACTIVATION BY FASL AND APO2L/TRAIL;819
18.25.15; TNFALPHA-INDUCED ACTIVATION OF NFKAPPAB PROTECTS AGAINST UV-INDUCED APOPTOSIS SPECIFICALLY IN P53-PROFICIENT CELLS;820
18.25.16; INFLUENCE OF OPTINEURIN ON ADENOVIRUS E3-14.7K MEDIATED TNF-RESISTANCE;821
18.25.17; CD137-INDUCED CELL DEATH IN PERIPHERAL BLOOD MONONUCLEAR CELLS;822
18.25.18; REGULATION OF CELL DEATH BY c-FLIP PHOSPHORYLATION;822
18.25.19; MATHEMATICAL MODELING OF APOPTOSIS AS A FUNCTION OF C-FLIP TURNOVER AND AT RANDOM PARAMETER DISTRIBUTIONS;823
18.25.20; RIP1, A JACK-OF-ALL-TRADES;824
19;Subject Index;825