title: Role of endoplasmic reticulum stress in rheumatoid arthritis pathogenesis.
abstract: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by abnormal proliferation of synoviocytes, leukocyte infiltration, and angiogenesis. The endoplasmic reticulum (ER) is the site of biosynthesis for all secreted and membrane proteins. The accumulation of unfolded proteins in the ER leads to a condition known as ER stress. Failure of the ER's adaptive capacity results in abnormal activation of the unfolded protein response. Recently, we have demonstrated that ER stress-associated gene signatures are highly expressed in RA synovium and synovial cells. Mice with Grp78 haploinsufficiency exhibit the suppression of experimentally induced arthritis, suggesting that the ER chaperone GRP78 is crucial for RA pathogenesis. Moreover, increasing evidence has suggested that GRP78 participates in antibody generation, T cell proliferation, and pro-inflammatory cytokine production, and is therefore one of the potential therapeutic targets for RA. In this review, we discuss the putative, pathophysiological roles of ER stress and GRP78 in RA pathogenesis.
authors.affiliation: Divsion of Rheumatology, Department of Internal Medicine, The Catholic University of Korea School of Medicine, Seoul, Korea.
authors.forename: Yune-Jung
authors.initials: YJ
authors.lastname: Park
authors.affiliation: Divsion of Rheumatology, Department of Internal Medicine, The Catholic University of Korea School of Medicine, Seoul, Korea.
authors.forename: Seung-Ah
authors.initials: SA
authors.lastname: Yoo
authors.affiliation: Divsion of Rheumatology, Department of Internal Medicine, The Catholic University of Korea School of Medicine, Seoul, Korea.
authors.forename: Wan-Uk
authors.initials: WU
authors.lastname: Kim
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000473:pathology*; D001323:Autoantibodies / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004721:Endoplasmic Reticulum / Q000276:immunology / Q000473:pathology; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000276:immunology*; D057895:Haploinsufficiency / Q000235:genetics; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D009389:Neovascularization, Pathologic / Q000235:genetics; D017510:Protein Folding; D013583:Synovial Membrane / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology; D056811:Unfolded Protein Response / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D016207:Cytokines; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse
keywords: Arhtritis; Endoplasmic Reticulum Stress; GRP78/BiP; Pathogenesis; Rheumatoid