ABBREVIATIONSCIAcollagen induced arthritisIRE1inositol‐requiting enzyme 1PERKprotein kinase R‐like endoplasmic reticulum kinaseRArheumatoid arthritisTACtacrolimusTGthapsigargin.IntroductionTacrolimus (TAC) is an immunosuppressive drug commonly used to lower the risk of rejection after allogeneic organ transplants. The 23‐membered macrolide lactone, isolated from the bacterium Streptomyces tsukubaensis, was first discovered in 1987. A potent calcineurin inhibitor, TAC is used in the treatment of T cell–mediated disease because it downregulates the synthesis of inflammatory cytokines by activated T cells. Several of these inflammatory cytokines, such as tumor necrosis factor alpha (TNF‐α), interleukin‐1 beta (IL‐1β), interleukin‐6 (IL‐6), and interferon‐c (Kino et al., ) are involved in mechanisms underlying rheumatoid arthritis (RA) pathogenesis (McDiarmid et al., ).Rheumatoid arthritis is a chronic inflammatory disease of unknown etiology characterized by symmetric, peripheral polyarthritis. It causes joint damage and physical disability. Bone erosion is a central feature of RA and is associated with poor functional outcomes (Gravallese and Goldring, ; Schett and Gravallese, ). The pathogenesis of RA is characterized by hyperactivity of osteoclasts, and is known to be associated with endoplasmic reticulum (ER) stress (Han et al., ; Murdoch et al., ; Shin et al., ). The ER is an organelle found in most eukaryotic cells that performs a variety of biological functions,
Cell Biology International – Wiley
Published: Jan 1, 2018
Keywords: ; ; ; ;
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