The p38 MAP kinase pathway as a therapeutic target in inflammatory disease

Curr Opin Pharmacol. 2004 Aug;4(4):372-7. doi: 10.1016/j.coph.2004.03.009.

Abstract

The p38 MAPK signalling pathway plays an important role in inflammation and other physiological processes. Specific inhibitors of p38 alpha and beta MAPK block production of the major inflammatory cytokines (i.e. tumour necrosis factor-alpha and interleukin-1) and other proteins (e.g. cyclooxygenase-2), and are anti-inflammatory in animal models of disease. A major function of the pathway is post-transcriptional control of inflammatory gene expression. Many of the mRNAs are unstable (or untranslatable) because of AU-rich elements in the 3'untranslated region. Signalling in the p38 pathway counteracts these and stabilizes the mRNAs by preventing their otherwise rapid de-adenylation.

Publication types

  • Review

MeSH terms

  • Animals
  • Enzyme Inhibitors / therapeutic use*
  • Humans
  • Inflammation / drug therapy*
  • Intracellular Signaling Peptides and Proteins
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinases / physiology
  • Protein-Serine-Threonine Kinases / physiology
  • Signal Transduction*
  • Transcription, Genetic
  • Tumor Necrosis Factor-alpha / genetics
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Enzyme Inhibitors
  • Intracellular Signaling Peptides and Proteins
  • Tumor Necrosis Factor-alpha
  • MAP-kinase-activated kinase 2
  • Protein-Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases