Prevention of excessive collagen accumulation by human intravenous immunoglobulin treatment in a murine model of bleomycin-induced scleroderma
Prevention of excessive collagen accumulation by human intravenous immunoglobulin treatment in a murine model of bleomycin-induced scleroderma
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DOI：
10.1111/j.1365-2249.2010.04295.x
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发表时间：
2011-02-01
影响因子：
4.6
通讯作者：
Nakae, T.
中科院分区：
文献类型：
--
作者：
Kajii, M.;Suzuki, C.;Nakae, T.
系统性硬化症（SSc）是一种自身免疫性疾病，其特征是皮肤和其他器官的纤维化变化，涉及过度的胶原沉积。在这里，我们研究了静脉注射免疫球蛋白（IVIG）对博莱霉素（BLM）诱导的硬皮病小鼠模型纤维化的影响。通过每天皮下注射BLM持续35天在C3 H/He J小鼠中诱导硬皮病。来自BLM注射组的皮肤样品中的胶原蛋白含量（6.30 +/-0.11 mg/g组织）显著高于PBS组（5.80 +/-0.10 mg/g组织），并且与注射部位的真皮增厚相对应。相比之下，在开始BLM注射后连续5天用IVIG处理的小鼠显示出显著较少的胶原蛋白含量（IVIG组，5.61 +/-0.09 mg/g组织; BLM对IVIG）。为了研究模型早期的细胞和蛋白质特征，在实验开始后7天获得皮肤样品。在BLM组中还观察到真皮巨噬细胞浸润、单核细胞趋化蛋白（MCP-1）阳性细胞和TGF-β 1 mRNA表达增加。IVIG抑制了这些早期纤维化变化; IVIG组的MCP-1表达（1.52 +/- 0.19 pg/mg组织）显著低于BLM组（2.49 +/- 0.26 pg/mg组织）。与此相反，TGF-β 1 mRNA的表达显着抑制IVIG。这些结果表明，IVIG治疗可以通过下调MCP-1和TGF-β的产生来抑制巨噬细胞向纤维化部位的募集，因此可能是用于管理纤维化疾病如SSc的潜在药物。
Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrotic changes in skin and other organs involving excessive collagen deposition. Here we investigated the effect of intravenous immunoglobulin (IVIG) on fibrosis in a murine model of bleomycin (BLM)-induced scleroderma. Scleroderma was induced in C3H/He J mice by subcutaneous BLM injections daily for 35 days. The collagen content in skin samples from the BLM-injected group (6.30 +/- 0.11 mg/g tissue) was significantly higher than the PBS group (5.80 +/- 0.10 mg/g tissue), and corresponded with dermal thickening at the injection site. In contrast, mice treated with IVIG for 5 consecutive days after initiating BLM injection showed lesser collagen content significantly (IVIG group, 5.61 +/- 0.09 mg/g tissue; BLM vs. IVIG). In order to investigate the cellular and protein characteristics in the early stage of the model, the skin samples were obtained 7 days after the onset of experiment. Macrophage infiltration to the dermis, monocyte chemoattractant protein (MCP-1)-positive cells, and increased TGF-beta 1 mRNA expression were also observed in the BLM group. IVIG inhibited these early fibrogenic changes; MCP-1 expression was significantly lesser for the IVIG group (1.52 +/- 0.19 pg/mg tissue) than for the BLM group (2.49 +/- 0.26 pg/mg tissue). In contrast, TGF-beta 1 mRNA expression was significantly inhibited by IVIG. These results suggest that IVIG treatment may inhibit macrophage recruitment to fibrotic sites by down regulating MCP-1 and TGF-beta production, and thus could be a potential drug for managing fibrotic disorders such as SSc.