title: Mitogen-activated protein kinases in innate immunity.
abstract: Following pathogen infection or tissue damage, the stimulation of pattern recognition receptors on the cell surface and in the cytoplasm of innate immune cells activates members of each of the major mitogen-activated protein kinase (MAPK) subfamilies--the extracellular signal-regulated kinase (ERK), p38 and Jun N-terminal kinase (JNK) subfamilies. In conjunction with the activation of nuclear factor-κB and interferon-regulatory factor transcription factors, MAPK activation induces the expression of multiple genes that together regulate the inflammatory response. In this Review, we discuss our current knowledge about the regulation and the function of MAPKs in innate immunity, as well as the importance of negative feedback loops in limiting MAPK activity to prevent host tissue damage. We also examine how pathogens have evolved complex mechanisms to manipulate MAPK activation to increase their virulence. Finally, we consider the potential of the pharmacological targeting of MAPK pathways to treat autoimmune and inflammatory diseases.
authors: Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK. j.s.c.arthur@dundee.ac.uk
authors: J Simon C
authors: JS
authors: Arthur
authors: Steven C
authors: SC
authors: Ley
mesh_terms: D000818:Animals; D004789:Enzyme Activation; D005246:Feedback; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007249:Inflammation / Q000201:enzymology / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000276:immunology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology
chemical_list: D051193:Toll-Like Receptors; D020928:Mitogen-Activated Protein Kinases
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