Allograft inflammatory factor-1 is overexpressed and induces fibroblast chemotaxis in the skin of sclerodermatous GVHD in a murine model.
Allograft inflammatory factor (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 pathogenic mechanism of fibrosis, we examined the expression and function of AIF in sclerodermatous (Scl) GVHD mice. 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 did not show 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.
Department of Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. kawahity@koto.kpu-m.ac.jp
Aihiro
A
Yamamoto
Eishi
E
Ashihara
Yoko
Y
Nakagawa
Hiroshi
H
Obayashi
Mitsuhiro
M
Ohta
Hirokazu
H
Hara
Tetsuo
T
Adachi
Takahiro
T
Seno
Masatoshi
M
Kadoya
Masahide
M
Hamaguchi
Hidetaka
H
Ishino
Masataka
M
Kohno
Taira
T
Maekawa
Yutaka
Y
Kawahito
D000818:Animals; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000276:immunology*; D002478:Cells, Cultured; D002633:Chemotaxis / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000276:immunology*; D020405:Dermis / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000276:immunology* / Q000378:metabolism; D006086:Graft vs Host Disease / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008840:Microfilament Proteins; D051381:Rats; D012595:Scleroderma, Systemic / Q000276:immunology* / Q000378:metabolism; D016038:Skin Transplantation; D014184:Transplantation, Homologous; D014945:Wound Healing / Q000276:immunology
C112986:AIF1 protein, human; C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; C508600:IL6 protein, human; D015850:Interleukin-6; D008840:Microfilament Proteins