The p38 MAPK Pathway in Rheumatoid Arthritis: A Sideways Look
Andrew R Clark*, Jonathan LE Dean
Identifiers and Pagination:Year: 2012
Issue: Suppl 2
First Page: 209
Last Page: 219
Publisher ID: TORJ-6-209
Article History:Received Date: 10/5/2012
Revision Received Date: 18/6/2012
Acceptance Date: 19/6/2012
Electronic publication date: 7/9/2012
Collection year: 2012
open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
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.