Role of human pulmonary fibroblast-derived MCP-1 in cell activation and migration in experimental silicosis
Role of human pulmonary fibroblast-derived MCP-1 in cell activation and migration in experimental silicosis
复制标题
人肺成纤维细胞衍生的 MCP-1 在实验性矽肺细胞活化和迁移中的作用。
DOI：
10.1016/j.taap.2015.07.002
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发表时间：
2015-10-15
影响因子：
3.8
通讯作者：
Chao, Jie
中科院分区：
文献类型：
--
作者：
Liu, Xueting;Fang, Shencun;Chao, Jie
背景：矽肺是由吸入二氧化硅(SiO_2)引起的全身性疾病。肺内二氧化硅的吞噬作用会引发炎症级联反应，导致成纤维细胞的增殖、迁移和随后的纤维化。临床证据表明，二氧化硅对肺泡巨噬细胞的激活可产生以单核细胞趋化蛋白-1(MCP-1)的产生为特征的快速而持久的炎症，从而导致纤维化。方法与结果：原代培养的成人肺成纤维细胞(HPF-a)经SiO_2处理后，MCP-1迅速而持久地被诱导，CC趋化因子受体2型(CC-R_2)蛋白水平升高，而特异性CCR_2抑制剂RS-102895可阻断SiO_2诱导的2D和3D培养体系中细胞活化和迁移的增加；结论：肺成纤维细胞来源的单核细胞趋化蛋白-1表达上调参与了二氧化硅诱导的肺成纤维细胞迁移。CCR2的表达也随着二氧化硅的增加而上调，这种上调促进了MCP-1对成纤维细胞的作用。我们的研究破译了成纤维细胞来源的单核细胞趋化蛋白-1和二氧化硅诱导的细胞迁移之间的联系。这一发现为单核细胞趋化蛋白-1在开发新的矽肺治疗策略方面的潜力提供了新的见解。(C)2015 Elsevier Inc.保留所有权利。
Background: Silicosis is a systemic disease caused by inhaling silicon dioxide (SiO2). Phagocytosis of SiO2 in the lung initiates an inflammatory cascade that results in fibroblast proliferation and migration and subsequent fibrosis. Clinical evidence indicates that the activation of alveolar macrophages by SiO2 produces rapid and sustained inflammation that is characterized by the generation of monocyte chemotactic protein 1 (MCP-1), which induces fibrosis. Pulmonary fibroblast-derived MCP-1 may play a critical role in fibroblast proliferation and migration.Methods and results: Experiments using primary cultured adult human pulmonary fibroblasts (HPF-a) demonstrated the following results: 1) SiO2 treatment resulted in the rapid and sustained induction of MCP-1 as well as the elevation of the CC chemokine receptor type 2 (CCR2) protein levels; 2) pretreatment of HPF-a with RS-102895, a specific CCR2 inhibitor, abolished the SiO2-induced increase in cell activation and migration in both 2D and 3D culture systems; and 3) RNA interference targeting CCR2 prevented the SiO2-induced increase in cell migration.Conclusion: These data demonstrated that the up-regulation of pulmonary fibroblast-derived MCP-1 is involved in pulmonary fibroblast migration induced by SiO2. CCR2 was also up-regulated in response to SiO2, and this up-regulation facilitated the effect of MCP-1 on fibroblasts. Our study deciphered the link between fibroblast-derived MCP-1 and SiO2-induced cell migration. This finding provides novel insight into the potential of MCP-1 in the development of novel therapeutic strategies for silicosis. (C) 2015 Elsevier Inc. All rights reserved.