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.
Immunol Lett. 2011 Mar 30;135(1-2):144-50. doi: 10.1016/j.imlet.2010.10.015. Epub 2010 Oct 30.
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.
同种异体炎症因子 (AIF)-1 已在大鼠心脏同种异体移植物的慢性排斥反应中被鉴定出，并被认为参与了免疫反应。我们之前表明，AIF-1 在类风湿关节炎的滑膜组织中强烈表达，rAIF-1 增加了滑膜细胞和外周血单核细胞的 IL-6 产生。最近，AIF-1 的表达已在系统性硬化症 (SSc) 组织中被报道，其临床特征和组织病理学与慢性移植物抗宿主病 (GVHD) 相似。为了阐明纤维化的发病机制，我们检查了 AIF 在硬皮病 GVHD 小鼠中的表达和功能。我们证明，与对照相比，在 Scl GVHD 小鼠增厚皮肤中浸润的单核细胞和成纤维细胞中，免疫反应性 AIF-1 和 IL-6 的表达明显增加。免疫组织化学发现通过 Western blot 分析得到证实。伤口愈合试验还表明 rAIF-1 直接增加正常人类真皮成纤维细胞 (NHDF) 的迁移，但细胞生长试验并未表明 rAIF-1 增加了它们的增殖。这些发现表明，AIF-1 可以诱导受影响皮肤组织中成纤维细胞的迁移和 IL-6 的产生，是促进 GVHD 纤维化的重要分子。尽管 AIF-1 的生物学功能尚未完全阐明，但 AIF-1 可以诱导单核细胞和成纤维细胞的趋化性并促进其分泌 IL-6。因此，AIF-1 可能为 SSc 以及 Scl GVHD 的抗纤维化治疗提供了一个有吸引力的新靶点。
