No conflicts of interest were declared.
TNF-mediated inflammatory disease†
Article first published online: 27 DEC 2007
Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Special Issue: Molecular and cellular themes in inflammation and immunology
Volume 214, Issue 2, pages 149–160, January 2008
How to Cite
Bradley, J. (2008), TNF-mediated inflammatory disease. J. Pathol., 214: 149–160. doi: 10.1002/path.2287
- Issue published online: 27 DEC 2007
- Article first published online: 27 DEC 2007
- NIHR Cambridge Biomedical Research Centre, UK
- tumour necrosis factor;
- signal transduction;
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.