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TNF‐mediated inflammatory disease
Author(s) -
Bradley JR
Publication year - 2008
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2287
Subject(s) - tumor necrosis factor alpha , inflammation , immunology , medicine , signal transduction , inflammatory bowel disease , ankylosing spondylitis , rheumatoid arthritis , psoriasis , cancer research , biology , disease , microbiology and biotechnology , pathology
Abstract TNF was originally described as a circulating factor that can cause necrosis of tumours, but has since been identified as a key regulator of the inflammatory response. This review describes the known signalling pathways and cell biological effects of TNF, and our understanding of the role of TNF in human disease. TNF interacts with two different receptors, designated TNFR1 and TNFR2, which are differentially expressed on cells and tissues and initiate both distinct and overlapping signal transduction pathways. These diverse signalling cascades lead to a range of cellular responses, which include cell death, survival, differentiation, proliferation and migration. Vascular endothelial cells respond to TNF by undergoing a number of pro‐inflammatory changes, which increase leukocyte adhesion, transendothelial migration and vascular leak and promote thrombosis. The central role of TNF in inflammation has been demonstrated by the ability of agents that block the action of TNF to treat a range of inflammatory conditions, including rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease and psoriasis. The increased incidence of infection in patients receiving anti‐TNF treatment has highlighted the physiological role of TNF in infectious diseases. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.