The p38alpha kinase plays a central role in inflammation.
The p38 kinase plays a central role in inflammation, and it has been the subject of extensive efforts in both basic research and drug discovery. This review summarizes the biology of the p38 kinase with a focus on its role in inflammation. The p38 kinase regulates the production of key inflammatory mediators by cells of the innate immune system, including TNFalpha, IL-1beta, and COX-2. In addition, p38 also acts downstream of cytokines such as TNFalpha, mediating some of their effects. Recently p38 has also been found to play a role in responses of T cells, including Th17 and regulatory T cells. Consistent with its important role in inflammation, recent evidence suggests cells may utilize a variety of feedback mechanisms to regulate and maintain p38 signal transduction. The biological processes regulated by p38 kinase suggest both a wide variety of potential indications for inhibitors and a level of complexity that has proven challenging to drug discovery efforts around this target.
Schieven
Gary L
GL
Immunology Drug Discovery, Research & Development, Bristol-Myers Squibb Princeton, NJ 08543, USA. Emailgary.schieven@bms.com
D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D004789:Enzyme Activation; D006801:Humans; D007249:Inflammation / Q000201:enzymology*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D047428:Protein Kinase Inhibitors; D048051:p38 Mitogen-Activated Protein Kinases