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肺炎链球菌肽链内切酶O(Pep O)是一种新发现的且广泛表达的肺炎链球菌毒力蛋白,帮助肺炎链球菌黏附侵袭入宿主细胞。我们的前期研究发现Pep O能诱导小鼠肺部强烈的固有免疫反应。但仍需进一步研究肺组织内识别Pep O的细胞。本实验中我们研究了Pep O对小鼠肺泡上皮细胞株MLE-12分泌的促炎性细胞因子IL-6及CXCL1的影响并研究了相关的信号通路。Pep O刺激MLE-12以剂量依赖的方式合成和释放IL-6、CXCL1。在Pep O激活的MLE-12细胞中我们同时检测到了TLR4 m RNA的上调。Pep O激活导致了MAPKs、P65和Akt的磷酸化,且MAPKs、IκB-α以及PI3K的抑制剂能降低IL-6以及CXCL1的分泌。这些结果提示我们Pep O以MAPKs-NF-κB-PI3K/Akt信号通路依赖的方式促进小鼠肺上皮细胞产生IL-6和CXCL1,在肺炎链球菌肺炎的病理形成中可能发挥着重要的作用。
Pneumococcal endopeptidase O (Pep O) is a newly discovered and widely expressed virulence factor of Streptococcus pneumoniae that assists adhesion and invasion of S. pneumoniae into host cells. Our previous study found that Pep O induced a strong innate immune response in the lungs of mice. However, further study is needed to identify Pep O-recognizing cells in lung tissue. In this experiment, we investigated the effects of Pep O on proinflammatory cytokines IL-6 and CXCL1 secreted by mouse alveolar epithelial cell line MLE-12 and investigated the related signaling pathways. Pep O stimulated MLE-12 to synthesize and release IL-6, CXCL1 in a dose-dependent manner. We also detected TLR4 mRNA upregulation in Pep O-activated MLE-12 cells. Pep O activation led to the phosphorylation of MAPKs, P65 and Akt, and inhibitors of MAPKs, IκB-α and PI3K decreased IL-6 and CXCL1 secretion. These results suggest that Pep O may promote the production of IL-6 and CXCL1 by mouse lung epithelial cells in a MAPKs-NF-|ÊB-PI3K / Akt signaling pathway and may play an important role in the pathological development of pneumococcal pneumonia.