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International Journal of Inflammation
Volume 2011, Article ID 580295, 5 pages
http://dx.doi.org/10.4061/2011/580295
Review Article

Myeloid-Related Protein Activity in Rheumatoid Arthritis

Division of Rheumatic Diseases, Department of Medicine, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, 2061 Cornell Road, Suite 207, Cleveland, OH 44106, USA

Received 14 March 2011; Revised 12 May 2011; Accepted 23 June 2011

Academic Editor: Rosario Scalia

Copyright © 2011 Charles J. Malemud. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

SA100A8, SA100A9, and SA100A12 are members of the myeloid-related protein class. SA100A8 and SA100A9, also known as MRP-8 and MRP-14, respectively, are intracellular Ca2+-binding proteins produced mainly by neutrophils and monocytes where they exist as a heterodimeric complex in the cytosol. The MRP-8/-14 complex has been shown to promote chronic inflammation associated with rheumatoid arthritis (RA). In that regard, MRP-8 and MRP-14 regulate the inflammatory response through their capacity to recruit neutrophils and monocytes to target tissues resulting in attachment to endothelium. MRPs also activate the signal transduction pathway principally involving the stress-activated/mitogen-activated protein kinases. MRP-8/MRP-14 also increased nitric oxide synthesis. Most recently, the MRP-8/MRP-14 complex was shown to be a novel ligand for the toll-like receptors (TLRs) and TLR-4, in particular. Engagement of TLRs by the MRP-8/-14 complex may be particularly important for activating antigen-presenting dendritic cells which regulate critical autoimmune responses that promote chronic synovitis characteristic of RA.