Role of galectin-3 in human pulmonary fibrosis.
Role of galectin-3 in human pulmonary fibrosis.
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DOI：
10.2332/allergolint.o-06-449
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发表时间：
2007-03-01
期刊：
影响因子：
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通讯作者：
Shirai, Koji
中科院分区：
文献类型：
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作者：
Nishi, Yumiko;Sano, Hideki;Shirai, Koji
背景技术背景：半乳糖凝集素-3（Galectin-3）是一种β-半乳糖苷结合蛋白，其参与多种生理和病理过程，包括人肝硬化和小鼠肺纤维化模型。本研究的目的是确定半乳糖凝集素3是否参与人肺纤维化。方法：我们测定了半乳糖凝集素3在支气管肺泡灌洗液（BALF）的浓度，并用ELISA和免疫组化染色分别检查其在间质性肺疾病患者肺泡巨噬细胞中的表达。使用单核/巨噬细胞系在体外，我们研究了半乳糖凝集素-3表达的细胞因子的影响，并通过RT-PCR和蛋白质印迹类似的相反。最后，我们进行了微Boyden室测定和Sircoll测定，以确定是否半乳糖凝集素-3诱导迁移和胶原合成，分别在fibroblast.Results：半乳糖凝集素-3是特别增加BALF从特发性肺纤维化（IPF）和间质性肺炎与胶原血管疾病（CVD-IP）的患者。接受皮质类固醇治疗的IPF和CVD-IP患者BALF中的半乳糖凝集素-3水平似乎较低。与对照组相比，IPF患者的肺泡巨噬细胞表达更多的半乳糖凝集素-3。在单核细胞系U937中，半乳糖凝集素-3的表达由肿瘤坏死因子-α（TNF-α）和干扰素（IFN）-γ诱导。半乳糖凝集素-3还诱导巨噬细胞系THP-1中TNF-α和白细胞介素（IL）-8的mRNA表达和蛋白质产生。这种凝集素刺激NIH-3 T3成纤维细胞诱导迁移和胶原合成in vitro.CONCLUSIONS：这些结果表明，galectin-3参与了人类IPF和CVD-IP的发病机制，通过激活巨噬细胞和成纤维细胞。
BACKGROUND: Galectin-3 is a beta-galactoside-binding protein which is implicated in diverse physiological and pathological processes including human liver cirrhosis and a mouse lung fibrosis model. The aim of this study is to determine whether galectin-3 is involved in human lung fibrosis.METHODS: We measured galectin-3 concentration in bronchoalveolar lavage fluid (BALF) and examined its expression in alveolar macrophages from patients with interstitial lung disorders using ELISA and immunohistochemical staining, respectively. Using monocyte/macrophage cell lines in vitro, we examined the effect of cytokines on galectin-3 expression, and the opposite similarly by RT-PCR and Western blotting. Finally, we performed Micro Boyden chamber assay and Sircoll assay to determine whether galectin-3 induces migration and collagen synthesis, respectively, in fibroblasts.RESULTS: Galectin-3 was specifically increased in BALF from patients with idiopathic pulmonary fibrosis (IPF) and interstitial pneumonia associated with collagen vascular disease (CVD-IP). Galectin-3 levels in BALF seemed to be lower in IPF and CVD-IP patients receiving corticosteroid therapy. Alveolar macrophages from IPF patients expressed more galectin-3 compared with those from control. Galectin-3 expression was induced by tumor necrosis factor-alpha (TNF-alpha) and interferon (IFN)-gamma in a monocytic cell line U937. Galectin-3 also induced mRNA expression and protein production of TNF-alpha and interleukin (IL)-8 in a macrophage cell line THP-1. This lectin stimulated NIH-3T3 fibroblast to induce migration and collagen synthesis in vitro.CONCLUSIONS: These results suggest that galectin-3 is involved in the pathogenesis of human IPF and CVD-IP by activating macrophages and fibroblasts.