title: IL-17 increases cadherin-11 expression in a model of autoimmune experimental arthritis and in rheumatoid arthritis.
abstract: IL-17 plays important roles in synovial inflammation and bone destruction in the mouse model of autoimmune arthritis and in rheumatoid arthritis (RA). Cadherin-11 determines the behavior of synovial cells in their proinflammatory and destructive tissue response in inflammatory arthritis, and promotes the invasive behavior of fibroblast-like synoviocytes (FLS). The purpose of this study was to examine the effect of IL-17 on the expression of cadherin-11 in autoimmune experimental arthritis and in RA synovium. The severity of synovial inflammation and bone destruction were examined in IL-17-injected knee joints of mice with collagen-induced arthritis (CIA). Cadherin-11 expression was examined in the synovium of mice with CIA, of IL-1 receptor antagonist (IL-1Ra)-deficient mice and of patients with RA and osteoarthritis (OA). Cadherin-11 expression was also examined in the synovium of IL-17 injected knee joints from CIA mice and in IL-17-stimulated FLS of CIA mice and RA patients. IL-17 aggravated synovial inflammation and bone destruction in CIA. By immunohistochemistry, cadherin-11 expression was increased in the synovium of mice with CIA and IL-1Ra-deficient mice and in patients with RA. Synovial cadherin-11 expression in IL-17-injected knee joints, measured by real-time RT-PCR, Western blot and immunohistochemistry, was increased in CIA. Cadherin-11 expression was significantly increased by IL-17 in cultured FLS of CIA mice and RA patients, and these increases were blocked by NF-κB inhibitors. IL-17 increased the expression of cadherin-11 in vivo and in vitro, which implies that an IL-17-induced increase of cadherin-11 is involved in IL-17-induced aggravation of joint destruction and inflammation.
authors.affiliation: Department of Internal Medicine, School of Medicine, Pusan National University, Busan, South Korea.
authors.forename: Young-Eun
authors.initials: YE
authors.lastname: Park
authors.forename: Yun-Ju
authors.initials: YJ
authors.lastname: Woo
authors.forename: Seong-Hu
authors.initials: SH
authors.lastname: Park
authors.forename: Young-Mee
authors.initials: YM
authors.lastname: Moon
authors.forename: Hye-Jwa
authors.initials: HJ
authors.lastname: Oh
authors.forename: Ju-In
authors.initials: JI
authors.lastname: Kim
authors.forename: Hua-Shu
authors.initials: HS
authors.lastname: Jin
authors.forename: Seung-Hoon
authors.initials: SH
authors.lastname: Baek
authors.forename: Geun-Tae
authors.initials: GT
authors.lastname: Kim
authors.forename: Jun-Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
authors.forename: Sung-Il
authors.initials: SI
authors.lastname: Kim
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D015551:Autoimmunity; D015820:Cadherins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D003094:Collagen / Q000008:administration & dosage; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics; D020381:Interleukin-17 / Q000008:administration & dosage*; D051379:Mice; D018345:Mice, Knockout; D013583:Synovial Membrane / Q000187:drug effects* / Q000378:metabolism
chemical_list: D015820:Cadherins; D053590:Interleukin 1 Receptor Antagonist Protein; D020381:Interleukin-17; C086960:osteoblast cadherin; D003094:Collagen