title: The role of glycoprotein 96 in the persistent inflammation of rheumatoid arthritis.
abstract: The 96-kDa glycoprotein (gp96) is an endoplasmic reticulum (ER) resident molecular chaperone. Under physiologic conditions, gp96 facilitates the transport of toll-like receptors (TLRs) to cell or endosomal membranes. Under pathologic circumstances such as rheumatoid arthritis, gp96 translocates to the cell surface and extracellular space, serving as an endogenous danger signal promoting TLR signaling. Macrophages play a central role in regulating innate and adaptive immunity, and are the major source of proinflammatory cytokines and chemokines in rheumatoid arthritis (RA). Macrophage numbers in the sublining of RA synovial tissue correlate with clinical response. This review focuses on the recent findings that implicate gp96 induced macrophage activation mediated through TLR signaling in the pathogenesis of RA and provides insights concerning the targeting gp96 and the TLR signaling pathway as therapeutic approaches for patients with RA and possibly other chronic inflammatory conditions.
authors.affiliation: Northwestern University Feinberg School of Medicine, Department of Medicine, Division of Rheumatology, 240 East Huron, McGaw M220, Chicago, IL 60611, USA. qqhuang@northwestern.edu
authors.forename: Qi-Quan
authors.initials: QQ
authors.lastname: Huang
authors.forename: Richard M
authors.initials: RM
authors.lastname: Pope
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D006360:Heat-Shock Proteins; D008562:Membrane Glycoproteins; D051193:Toll-Like Receptors; C053387:endoplasmin