Abstract
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 TNFα, IL-1β, and COX-2. In addition, p38 also acts downstream of cytokines such as TNFα, 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.
Current Topics in Medicinal Chemistry
Title: The p38α Kinase Plays a Central Role In Inflammation
Volume: 9 Issue: 11
Author(s): Gary L. Schieven
Affiliation:
Abstract: 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 TNFα, IL-1β, and COX-2. In addition, p38 also acts downstream of cytokines such as TNFα, 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.
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Schieven L. Gary, The p38α Kinase Plays a Central Role In Inflammation, Current Topics in Medicinal Chemistry 2009; 9 (11) . https://dx.doi.org/10.2174/156802609789630974
DOI https://dx.doi.org/10.2174/156802609789630974 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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