Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.
Department of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin, 300211, China.
Int J Med Microbiol. 2019 Dec;309(8):151340. doi: 10.1016/j.ijmm.2019.151340. Epub 2019 Aug 19.
Chlamydia pneumoniae (C. pneumoniae) infection is associated with the initiation and progression of atherosclerosis. The migration of vascular smooth muscle cell (VSMC) from the media to the intima is a key event in the development of atherosclerosis. Interleukin-17C (IL-17C) could enhance cell migration ability. The aim of our study is to investigate the role of IL-17C in C. pneumoniae infection-promoted VSMC migration, thereby possibly accelerating atherosclerosis. We firstly demonstrated that C. pneumoniae infection significantly increased IL-17C expression in VSMCs in the atherosclerotic lesion area from ApoE deficient mice. Our in vitro study further showed that IL-17C is required for C. pneumoniae infection-promoted VSMC migration, and its expression could be regulated by c-Fos through phosphorylating extracellular signal-regulated kinase (ERK). Unexpectedly, in the present study, we also found that IL-17C is critical for C. pneumoniae infection-induced c-Fos activation. c-Fos expression and activation induced by the exposure to recombinant IL-17C were markedly suppressed in the presence of the ERK inhibitor PD98059. These results suggest a possible positive feedback between c-Fos and IL-17C after C. pneumoniae infection. Taken together, our results indicate that C. pneumoniae infection promotes VSMC migration via c-Fos/IL-17C signaling.
肺炎衣原体（C. pneumoniae）感染与动脉粥样硬化的发生和发展有关。血管平滑肌细胞（VSMC）从中膜向内膜迁移是动脉粥样硬化发展的关键事件。白细胞介素-17C（IL-17C）可以增强细胞迁移能力。本研究旨在探讨 IL-17C 在 C. pneumoniae 感染促进 VSMC 迁移中的作用，从而可能加速动脉粥样硬化的发生。我们首先证明，在载脂蛋白 E 缺陷小鼠的动脉粥样硬化病变区域，C. pneumoniae 感染显著增加了 VSMCs 中的 IL-17C 表达。我们的体外研究进一步表明，IL-17C 是 C. pneumoniae 感染促进 VSMC 迁移所必需的，其表达可以通过 c-Fos 磷酸化细胞外信号调节激酶（ERK）来调节。出乎意料的是，在本研究中，我们还发现 IL-17C 对于 C. pneumoniae 感染诱导的 c-Fos 激活至关重要。在存在 ERK 抑制剂 PD98059 的情况下，重组 IL-17C 暴露引起的 c-Fos 表达和激活明显受到抑制。这些结果表明，C. pneumoniae 感染后 c-Fos 和 IL-17C 之间可能存在正反馈。综上所述，我们的研究结果表明，C. pneumoniae 感染通过 c-Fos/IL-17C 信号通路促进 VSMC 迁移。
