Xing Xiaojing, Yang Ji, Yang Xiaoqin, Wei Yi, Zhu Lubing, Gao Di, Li Ming
Department of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, China.
PLoS One. 2013 Dec 23;8(12):e85032. doi: 10.1371/journal.pone.0085032. eCollection 2013.
Recent reports have demonstrated that endothelial cells are involved in vascular inflammatory injury in systemic sclerosis (SSc) and interleukin-17A (IL-17A) plays a crucial role in the pathogenesis of SSC. However, little is known about the effects of IL-17A on endothelial cell inflammation in SSC. The aim of our study was to investigate the role of IL-17A in endothelial inflammation. Here, we showed that IL-17A mRNA and protein levels were augmented in the peripheral blood and more IL-17⁺ lymphocytes infiltrated in the perivascular areas in the involved skin of SSC patients. SSC patient serum induced chemokine and adhesion molecule expression in HUVECs, which was blocked by IL-17A neutralization. IL-17A alone induced chemokine and adhesion molecule expression and promoted T cell-HUVEC adhesion. Extracellular signal-regulated kinase (ERK) inhibition and IL-17A neutralization prominently inhibited chemokine and adhesion molecule expression and blocked T cell-HUVEC adhesion. IL-17A derived from SSC patient serum mediated endothelial cells inflammation by up-regulating chemokines and adhesion molecules, which was blocked by ERK inhibition. These data imply that ERK signal pathway might play a key role in the progression of endothelial injury induced by IL-17A in SSC.
近期报告显示，内皮细胞参与系统性硬化症（SSc）的血管炎性损伤，且白细胞介素-17A（IL-17A）在SSc发病机制中起关键作用。然而，关于IL-17A对SSc中内皮细胞炎症的影响知之甚少。我们研究的目的是探讨IL-17A在内皮炎症中的作用。在此，我们发现SSc患者外周血中IL-17A的mRNA和蛋白水平升高，且更多的IL-17⁺淋巴细胞浸润于受累皮肤的血管周围区域。SSc患者血清可诱导人脐静脉内皮细胞（HUVECs）中趋化因子和黏附分子的表达，而这种诱导作用可被IL-17A中和所阻断。单独的IL-17A可诱导趋化因子和黏附分子的表达，并促进T细胞与HUVECs的黏附。细胞外信号调节激酶（ERK）抑制和IL-17A中和显著抑制趋化因子和黏附分子的表达，并阻断T细胞与HUVECs的黏附。SSc患者血清来源的IL-17A通过上调趋化因子和黏附分子介导内皮细胞炎症，而这种作用可被ERK抑制所阻断。这些数据表明，ERK信号通路可能在SSc中IL-17A诱导的内皮损伤进展中起关键作用。
