Role of TNF in pathologies induced by nuclear factor kappaB deficiency.
TNF is a potent cytokine with an important role in the regulation of a multitude of cellular responses and in coordinating immune and inflammatory reactions. TNF exerts its effects by binding to the TNFR1- and TNFR2-specific cell surface receptors, which activate a number of intracellular signaling cascades including the nuclear factor kappaB (NF-kappaB) and mitogen-activated protein kinase pathways. Activation of NF-kappaB mediates many of the functions of TNF by transmitting information from the cell surface TNF receptors to the nucleus, where it coordinates a gene expression program that allows the cell to survive and elicit its responses. The intimate interplay of TNF with the NF-kappaB signaling pathway is highlighted by results obtained in transgenic and knockout mice with defects in NF-kappaB signaling components, where TNF has been shown to contribute to different pathologies observed in these mice. This chapter focuses on the function of TNF in pathologies induced by NF-kappaB deficiency and discusses the implications of these findings for our understanding of inflammatory diseases.
Vlantis
Katerina
K
Centre for Molecular Medicine and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, Institute of Genetics, University of Cologne, Zülpicher Strasse 47, Cologne, Germany.
Pasparakis
Manolis
M
D000818:Animals; D004064:Digestive System / Q000276:immunology / Q000473:pathology; D005260:Female; D005333:Fetus / Q000276:immunology / Q000473:pathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D016328:NF-kappa B / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D011247:Pregnancy; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000502:physiology
D047908:Intracellular Signaling Peptides and Proteins; C514981:NEMO protein, mouse; D016328:NF-kappa B; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha