TNF, cell death and inflammation
Journal Article (Review;Journal)
Tumor necrosis factor (TNFα) is a pleiotropic cytokine that mediates diverse biological responses. In the immune system, TNFα facilitates many aspects of immune responses against pathogenic challenges. While TNFα plays a critical role in the immune defense against pathogens, hyper-activation of the TNFα signaling cascade often results in the development of inflammatory and autoimmune diseases. Examination of natural mutations in human and experimental mouse models that affect TNFα-TNF receptor interaction or their downstream signaling components confirm the importance of this cytokine /receptor pair in the inflammatory process and immunity. Blockade of TNF-TNF receptor interaction has been highly successful in treating several autoimmune diseases including rheumatoid arthritis and Crohn's disease. The pro-inflammatory effects of TNFα can be achieved through several distinct signaling mechanisms including the activation of NF-κB and programmed cell death. In this review, we discuss recent advances in our understanding of the mechanisms by which TNFα induces different forms of programmed cell death and the role they play in mediating the inflammatory response. Specifically, we discuss how the induction of a recently defined cell death pathway, programmed necrosis, by TNFα may contribute to the activation of innate immune responses and the inflammatory process. © 2005 Bentham Science Publishers Ltd.
Full Text
Duke Authors
Cited Authors
- Bixby, J; Ray, TD; Chan, FKM
Published Date
- January 1, 2005
Published In
Volume / Issue
- 4 / 6
Start / End Page
- 557 - 567
International Standard Serial Number (ISSN)
- 1568-0142
Digital Object Identifier (DOI)
- 10.2174/156801405774933214
Citation Source
- Scopus