title: Synergy between adiponectin and interleukin-1β on the expression of interleukin-6, interleukin-8, and cyclooxygenase-2 in fibroblast-like synoviocytes.
abstract: To determine whether adiponectin may have synergistic effects in combination with the proinflammatory cytokine interleukin (IL)-1β regarding the production of proinflammatory mediators during arthritic joint inflammation, synovial cells from rheumatoid arthritis (RA) patients were treated with adiponectin, IL-1β, and their combination for 24 h. Culture supernatant was collected and analyzed by enzyme-linked immunosorbent assay for levels of IL-6, IL-8, prostaglandin E(2) (PGE(2)), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs). Adiponectin-mediated intracellular signaling pathways were investigated to elucidate the molecular mechanisms underlying their synergy. The association of proinflammatory mediators with adiponectin was investigated in the synovial fluid of arthritis patients. Adiponectin functioned synergistically with IL-1β to activate IL-6, IL-8, and PGE2 expression in RA fibroblast-like synoviocytes; Levels of VEGF, MMP-1, and MMP-13 were not synergistically stimulated. Adiponectin and IL-1β each increased the expression of both adiponectin receptor 1 and IL-1 receptor 1. However, adiponectin and IL-1β did not synergistically support the degradation of IκB-α or the nuclear translocation of NF-κB. Synergistically increased gene expression was significantly inhibited by MG132, an NF-κB inhibitor. Supporting the in vitro results, IL-6 and IL-8 levels were positively associated with adiponectin in synovial joint fluid from patients with RA, but not osteoarthritis (OA). In conclusion, adiponectin and IL-1β may synergistically stimulate the production of proinflammatory mediators through unknown signaling pathways during arthritic joint inflammation. Adiponectin may be more important to the pathogenesis of RA than previously thought.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, School of Medicine, Kyung Hee University, Seoul 130-701, Korea.
authors.forename: Yeon-Ah
authors.initials: YA
authors.lastname: Lee
authors.forename: Hyun Mi
authors.initials: HM
authors.lastname: Choi
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Hyung-In
authors.initials: HI
authors.lastname: Yang
authors.forename: Myung Chul
authors.initials: MC
authors.lastname: Yoo
authors.forename: Seung-Jae
authors.initials: SJ
authors.lastname: Hong
authors.forename: Kyoung Soo
authors.initials: KS
authors.lastname: Kim
mesh_terms: D052242:Adiponectin / Q000008:administration & dosage / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000008:administration & dosage / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007596:Joints / Q000378:metabolism / Q000473:pathology; D020782:Matrix Metalloproteinases; D016328:NF-kappa B / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D010003:Osteoarthritis; D054419:Receptors, Adiponectin / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D013582:Synovial Fluid / Q000166:cytology / Q000378:metabolism
chemical_list: C475418:ADIPOR1 protein, human; D052242:Adiponectin; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D054419:Receptors, Adiponectin; D017472:Receptors, Interleukin-1; D051546:Cyclooxygenase 2; D020782:Matrix Metalloproteinases