The p38 MAP kinase pathway as a therapeutic target in inflammatory disease.
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.
Saklatvala
Jeremy
J
Kennedy Institute of Rheumatology, Imperial College Faculty of Medicine, 1 Aspenlea Road, London W6 8LH, UK. j.saklatvala@imperial.ac.uk
D000818:Animals; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D047908:Intracellular Signaling Peptides and Proteins; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D015398:Signal Transduction; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2
D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D020928:Mitogen-Activated Protein Kinases; D017346:Protein Serine-Threonine Kinases; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2