Department of Respiration, Shanghai Sixth People's Hospital East Affiliated to Shanghai University of Medicine & Health Sciences, Shanghai, China.
Can Respir J. 2019 Jul 10;2019:2697376. doi: 10.1155/2019/2697376. eCollection 2019.
The transmembrane chemokine (C-X-C motif) ligand 16 (CXCL16) plays a vital role in the pathogenesis of organ fibrosis, including the liver and kidney. However, the detailed biological function of CXCL16 is still not fully understood in the progression of pulmonary fibrosis (PF). The aim of present study is to examine the function of CXCL16 in PF.
In this study, we constructed the PF model on mouse by using bleomycin and analyzed the effect of the mouse recombinant protein CXCL16 on mouse lung fibroblast L929 (LF) as well. To further examine the connection between CXCL16 and STAT3 in mouse LF cells, the STAT3 inhibitor AG490 was utilized to inhibit the expression of STAT3. Meanwhile, lipopolysaccharide was used to enhance the phosphorylation of STAT3 (p-STAT3) in mouse LF cells.
Our results indicated that the level of CXCL16/CXCR6 was significantly upregulated in the mouse PF model. Moreover, the level of p-STAT3 was also promoted. In addition, the mouse recombinant protein CXCL16 not only contributed to the proliferation of mouse LF cells but also induced the expression of p-STAT3 in LF cells. However, the effect of CXCL16 was deeply abolished by the STAT3 inhibitor AG490 in LF cells. Meanwhile, the antibody of CXCL16 deeply reduced the phosphorylation of STAT3 in lipopolysaccharide (LPS) cultured cells.
All these results demonstrated that CXCL16 promoted the phosphorylation of STAT3 and further demonstrated that STAT3 was a critical component in CXCL16/CXCR6 signaling pathway. This research not only enhanced the comprehension of CXCL16 but also indicated its potential value as a target in the treatment for human PF.
趋化因子（C-X-C 基序）配体 16（CXCL16）在器官纤维化的发病机制中发挥着重要作用，包括肝脏和肾脏。然而，在肺纤维化（PF）的进展中，CXCL16 的详细生物学功能仍不完全清楚。本研究旨在研究 CXCL16 在 PF 中的作用。
本研究通过使用博来霉素构建了 PF 小鼠模型，并分析了小鼠重组蛋白 CXCL16 对小鼠肺成纤维细胞 L929（LF）的影响。为了进一步研究 CXCL16 与 STAT3 在小鼠 LF 细胞中的关系，使用 STAT3 抑制剂 AG490 抑制 STAT3 的表达。同时，脂多糖被用于增强小鼠 LF 细胞中 STAT3 的磷酸化（p-STAT3）。
我们的结果表明，在 PF 小鼠模型中，CXCL16/CXCR6 水平显著上调。此外，p-STAT3 的水平也得到了促进。此外，小鼠重组蛋白 CXCL16 不仅促进了小鼠 LF 细胞的增殖，还诱导了 LF 细胞中 p-STAT3 的表达。然而，在 LF 细胞中，STAT3 抑制剂 AG490 深度抑制了 CXCL16 的作用。同时，CXCL16 的抗体在脂多糖（LPS）培养的细胞中深度降低了 STAT3 的磷酸化。
所有这些结果表明，CXCL16 促进了 STAT3 的磷酸化，并进一步表明 STAT3 是 CXCL16/CXCR6 信号通路的关键组成部分。本研究不仅增强了对 CXCL16 的理解，还表明其作为人类 PF 治疗靶点的潜在价值。
