title: A critical role for allograft inflammatory factor-1 in the pathogenesis of rheumatoid arthritis.
abstract: Rheumatoid arthritis (RA) is characterized by massive synovial proliferation, angiogenesis, subintimal infiltration of inflammatory cells and the production of cytokines such as TNF-alpha and IL-6. Allograft inflammatory factor-1 (AIF-1) has been identified in chronic rejection of rat cardiac allografts as well as tissue inflammation in various autoimmune diseases. AIF-1 is thought to play an important role in chronic immune inflammatory processes, especially those involving macrophages. In the current work, we examined the expression of AIF-1 in synovial tissues and measured AIF-1 in synovial fluid (SF) derived from patients with either RA or osteoarthritis (OA). We also examined the proliferation of synovial cells and induction of IL-6 following AIF-1 stimulation. Immunohistochemical staining showed that AIF-1 was strongly expressed in infiltrating mononuclear cells and synovial fibroblasts in RA compared with OA. Western blot analysis and semiquantitative RT-PCR analysis demonstrated that synovial expression of AIF-1 in RA was significantly greater than the expression in OA. AIF-1 induced the proliferation of cultured synovial cells in a dose-dependent manner and increased the IL-6 production of synovial fibroblasts and PBMC. The levels of AIF-1 protein were higher in synovial fluid from patients with RA compared with patients with OA (p < 0.05). Furthermore, the concentration of AIF-1 significantly correlated with the IL-6 concentration (r = 0.618, p < 0.01). These findings suggest that AIF-1 is closely associated with the pathogenesis of RA and is a novel member of the cytokine network involved in the immunological processes underlying RA.
authors.affiliation: Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, Japan.
authors.forename: Mizuho
authors.initials: M
authors.lastname: Kimura
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kawahito
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Obayashi
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Ohta
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Hara
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Adachi
authors.forename: Daisaku
authors.initials: D
authors.lastname: Tokunaga
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Hojo
authors.forename: Masahide
authors.initials: M
authors.lastname: Hamaguchi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Omoto
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Ishino
authors.forename: Makoto
authors.initials: M
authors.lastname: Wada
authors.forename: Masataka
authors.initials: M
authors.lastname: Kohno
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Tsubouchi
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000276:immunology; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008297:Male; D008840:Microfilament Proteins; D008875:Middle Aged; D010003:Osteoarthritis / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D013582:Synovial Fluid / Q000276:immunology / Q000378:metabolism*
chemical_list: C112986:AIF1 protein, human; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D008840:Microfilament Proteins