1.UMR 7355 Molecular and Experimental Immunology and Neurogenetics, 3B rue de la Férollerie, 45071 Orléans Cedex 2, France.
J Leukoc Biol. 2013 Dec;94(6):1317-23. doi: 10.1189/jlb.0313140. Epub 2013 Aug 23.
IPF is a chronic, progressive pulmonary disease, leading to respiratory failure. In search of mechanisms of IPF, we used the bleomycin-induced lung-injury model in mice, which causes acute inflammation that may progress to chronic lung inflammation and fibrosis. Here, we asked whether CXCL6/GCP-2, a member of the CXC chemokine superfamily, may be involved in IPF development. First, we reported an increase of CXCL6 levels in BALF from patients with IPF, as well as in the lung of mice, 24 h after bleomycin administration. To investigate whether CXCL6 played a role in experimental bleomycin-induced pulmonary fibrosis, we treated mice with an anti-mCXCL6 mAb that has been shown to inhibit neutrophil chemotaxis in vitro. CXCL6 antibody blockade attenuated acute inflammation with a reduced pulmonary neutrophil influx, IL-1β, CXCL1, and TIMP-1 production. In the later phase (14 days after bleomycin exposure), lymphocyte recruitment and fibrosis markers, such as collagen and TIMP-1, were diminished, as well as collagen deposition and fibrotic lesion the lung. Therefore, the data suggest that CXCL6 contributes to experimental pulmonary fibrosis, and CXCL6 inhibition might be used to reduce lung toxicity associated with bleomycin treatment.
特发性肺纤维化（IPF）是一种慢性、进行性的肺部疾病，可导致呼吸衰竭。为了探索 IPF 的发病机制，我们使用博来霉素诱导的小鼠肺损伤模型，该模型可引起急性炎症，进而发展为慢性肺炎症和纤维化。在这里，我们探讨了趋化因子（CXC 亚家族）配体 6/生长调节致癌基因β（CXCL6/GCP-2）是否参与 IPF 的发生。首先，我们报道了 IPF 患者 BALF 以及博来霉素处理 24 h 后小鼠肺中 CXCL6 水平增加。为了研究 CXCL6 在实验性博来霉素诱导的肺纤维化中的作用，我们用抗 mCXCL6 mAb 处理小鼠，该 mAb 已被证明可抑制体外中性粒细胞趋化。CXCL6 抗体阻断减轻了急性炎症，减少了肺中性粒细胞浸润、IL-1β、CXCL1 和 TIMP-1 的产生。在后期（博来霉素暴露后 14 天），淋巴细胞募集和纤维化标志物（如胶原蛋白和 TIMP-1）减少，胶原沉积和纤维化病变减轻。因此，这些数据表明 CXCL6 参与了实验性肺纤维化，CXCL6 抑制可能用于减少与博来霉素治疗相关的肺毒性。
