The p38alpha kinase plays a central role in inflammation

Curr Top Med Chem. 2009;9(11):1038-48. doi: 10.2174/156802609789630974.


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.

Publication types

  • Review

MeSH terms

  • Arthritis, Rheumatoid / drug therapy
  • Enzyme Activation
  • Humans
  • Inflammation / enzymology*
  • Protein Kinase Inhibitors / therapeutic use
  • Signal Transduction
  • p38 Mitogen-Activated Protein Kinases / metabolism*


  • Protein Kinase Inhibitors
  • p38 Mitogen-Activated Protein Kinases