BACKGROUND: Interleukin (IL)-36α is a recently described member of the IL-1 cytokine family with pro-inflammatory and clearly pathogenic properties in psoriasis. OBJECTIVE: To determine the IL-36α expression in psoriatic arthritis (PsA) compared to rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Synovial tissues obtained from arthritis patients were stained for IL-36α, IL-36 receptor (IL-36R) and IL-36R antagonist (IL-36Ra) by immunohistochemistry and immunofluorescence. Lysates were examined for IL-36α by western blot analysis. Synovial fibroblasts (FLS) cultured in the presence of IL-36α were assayed for cytokine expression by quantitative real time PCR and multiplex assay. IL-36α-induced signal transduction in FLS was analysed by immunoblotting. RESULTS: Expression of IL-36R and its ligands IL-36α and IL-36Ra was detected in the synovial lining layer and cellular infiltrates of patients with inflammatory arthritis. IL-36α was expressed significantly higher in PsA and RA than in OA synovium. CD138-positive plasma cells were identified as the main cellular source of IL-36α. No differences were observed for the expression of IL-36R and IL-36Ra between PsA, RA and OA. Functionally, IL-36α induced the expression of IL-6 and IL-8 in FLS through p38/NFkB activation. CONCLUSIONS: IL-36α is up-regulated in PsA and RA synovium, expressed by tissue plasma cells and leads to IL-6 and IL-8 production by synovial fibroblasts. Hence, IL-36α links plasma cells to inflammatory cytokine production by FLS and may represent a key link between autoimmunity and the induction of synovitis.
BACKGROUND: Interleukin (IL)-36α is a recently described member of the IL-1 cytokine family with pro-inflammatory and clearly pathogenic properties in psoriasis. OBJECTIVE: To determine the IL-36α expression in psoriatic arthritis (PsA) compared to rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Synovial tissues obtained from arthritispatients were stained for IL-36α, IL-36 receptor (IL-36R) and IL-36R antagonist (IL-36Ra) by immunohistochemistry and immunofluorescence. Lysates were examined for IL-36α by western blot analysis. Synovial fibroblasts (FLS) cultured in the presence of IL-36α were assayed for cytokine expression by quantitative real time PCR and multiplex assay. IL-36α-induced signal transduction in FLS was analysed by immunoblotting. RESULTS: Expression of IL-36R and its ligands IL-36α and IL-36Ra was detected in the synovial lining layer and cellular infiltrates of patients with inflammatory arthritis. IL-36α was expressed significantly higher in PsA and RA than in OA synovium. CD138-positive plasma cells were identified as the main cellular source of IL-36α. No differences were observed for the expression of IL-36R and IL-36Ra between PsA, RA and OA. Functionally, IL-36α induced the expression of IL-6 and IL-8 in FLS through p38/NFkB activation. CONCLUSIONS: IL-36α is up-regulated in PsA and RA synovium, expressed by tissue plasma cells and leads to IL-6 and IL-8 production by synovial fibroblasts. Hence, IL-36α links plasma cells to inflammatory cytokine production by FLS and may represent a key link between autoimmunity and the induction of synovitis.
Authors: F Ciccia; A Accardo-Palumbo; R Alessandro; C Alessandri; R Priori; G Guggino; S Raimondo; F Carubbi; G Valesini; R Giacomelli; A Rizzo; G Triolo Journal: Clin Exp Immunol Date: 2015-06-03 Impact factor: 4.330
Authors: Garrett J Patrick; Haiyun Liu; Martin P Alphonse; Dustin A Dikeman; Christine Youn; Jack C Otterson; Yu Wang; Advaitaa Ravipati; Momina Mazhar; George Denny; Roger V Ortines; Emily Zhang; Robert J Miller; Carly A Dillen; Qi Liu; Sabrina J Nolan; Kristine Nguyen; LeeAnn Marcello; Danh C Do; Eric M Wier; Yan Zhang; Gary Caviness; Alexander C Klimowicz; Diane V Mierz; Jay S Fine; Guangping Sun; Raphaela Goldbach-Mansky; Alina I Marusina; Alexander A Merleev; Emanual Maverakis; Luis A Garza; Joshua D Milner; Peisong Gao; Meera Ramanujam; Ernest L Raymond; Nathan K Archer; Lloyd S Miller Journal: J Clin Invest Date: 2021-03-01 Impact factor: 14.808
Authors: Sol Kim; Drake W Williams; Cindy Lee; Terresa Kim; Atsushi Arai; Songtao Shi; Xinmin Li; Ki-Hyuk Shin; Mo K Kang; No-Hee Park; Reuben H Kim Journal: J Bone Miner Res Date: 2016-10-12 Impact factor: 6.741
Authors: M-A Boutet; G Bart; M Penhoat; J Amiaud; B Brulin; C Charrier; F Morel; J-C Lecron; M Rolli-Derkinderen; A Bourreille; S Vigne; C Gabay; G Palmer; B Le Goff; F Blanchard Journal: Clin Exp Immunol Date: 2016-02-22 Impact factor: 4.330