Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Allograft Inflammatory Factor-1 Facilitates the Migration of Fibroblasts and Has a Correlation with the Pathogensis of Skin Fibrosis in a Murine Model of a Murine Model of Sclerodermatous GVHD.
Yamamoto1, Aihiro, Ashihara2, Eishi, Nakagawa2, Yoko, Obayashi3, Hiroshi, Seno1, Takahiro, Kadoya1, Masatoshi, Hamaguchi1, Masahide
Department of Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital
Institute of Bio-Response Informatics
Allograft inflammatory factor (AIF)-1 is an IFN-g-inducible, Ca2+- binding EF-hand protein that is encoded within the HLA class III genomic region in the direct vicinity of TNF-a. AIF-1 has been identified in chronic rejection of rat cardiac allografts and is thought to be involved in the immune response. We previously showed that AIF-1 was strongly expressed in synovial tissues in rheumatoid arthritis and that rAIF-1 increased the IL-6 production of synoviocytes and peripheral blood mononuclear cells. Recently, the expression of AIF-1 has been reported in systemic sclerosis (SSc) tissues, whose clinical features and histopathology are similar to those of chronic graft-vs-host disease (GVHD). To clarify the pathomechanism of fibrosis, we underwent bone marrow transplantation and made sclerodermatous (Scl) GVHD mice. We examined the expression and function of AIF in Scl GVHD mice on day 21 after BMT. We demonstrated that immunoreactive AIF-1 and IL-6 were significantly expressed in infiltrating mononuclear cells and fibroblasts in thickened skin of Scl GVHD mice compared with control. The immunohistochemical findings were confirmed by Western blot analysis. Wound healing assay also revealed that rAIF-1 increased the migration of normal human dermal fibroblasts (NHDF) directly, but cell growth assay didn't showed that rAIF-1 increased the proliferation of them. These findings suggest that AIF-1, which can induce the migration of fibroblasts and the production of IL-6 in affected skin tissues, is an important molecule promoting fibrosis in GVHD. Although the biological function of AIF-1 has not been completely elucidated, AIF-1 can induce IL-6 secretion on mononuclear cells and fibroblast chemotaxis. AIF-1 may accordingly provide an attractive new target for antifibrotic therapy in SSc as well as Scl GVHD.
To cite this abstract, please use the following information:
Yamamoto, Aihiro, Ashihara, Eishi, Nakagawa, Yoko, Obayashi, Hiroshi, Seno, Takahiro, Kadoya, Masatoshi, et al; Allograft Inflammatory Factor-1 Facilitates the Migration of Fibroblasts and Has a Correlation with the Pathogensis of Skin Fibrosis in a Murine Model of a Murine Model of Sclerodermatous GVHD. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1511