The p38 MAPK pathway in rheumatoid arthritis: A sideways look

Research output: Contribution to journalReview article

Authors

Colleges, School and Institutes

External organisations

  • Imperial College London

Abstract

The p38 mitogen-activated protein kinase (MAPK) signaling pathway has been strongly implicated in many of the processes that underlie the pathology of rheumatoid arthritis (RA). For many years it has been considered a promising target for development of new anti-inflammatory drugs with which to treat RA and other chronic immune-mediated inflammatory diseases. However, several recent clinical trials have concluded in a disappointing manner. Why is this so, if p38 MAPK clearly contributes to the excessive production of inflammatory mediators, the destruction of bone and cartilage? We argue that, to explain the apparent failure of p38 inhibitors in the rheumatology clinic, we need to understand better the complexities of the p38 pathway and its many levels of communication with other cellular signaling pathways. In this review we look at the p38 MAPK pathway from a slightly different perspective, emphasising its role in post-transcriptional rather than transcriptional control of gene expression, and its contribution to the off-phase rather than the on-phase of the inflammatory response.

Details

Original languageEnglish
Pages (from-to)209-219
Number of pages11
JournalOpen Rheumatology Journal
Volume6
Issue numberSPEC. ISSUE 2
Publication statusPublished - 18 Dec 2012

Keywords

  • Gene expression, Inflammatory mediators, Listeria monocytogenes, P38 MAPK, Phosphorylation

ASJC Scopus subject areas