Aspergillus fumigatus Increased PAR-2 Expression and Elevated Proinflammatory Cytokines Expression Through the Pathway of PAR-2/ERK1/2 in Cornea
Aspergillus fumigatus Increased PAR-2 Expression and Elevated Proinflammatory Cytokines Expression Through the Pathway of PAR-2/ERK1/2 in Cornea
复制标题
烟曲霉通过 PAR-2/ERK1/2 途径增加角膜中 PAR-2 的表达并升高促炎细胞因子的表达
DOI：
10.1167/iovs.17-21887
复制
发表时间：
2018-01-01
影响因子：
4.4
通讯作者：
Xu, Qiang
中科院分区：
文献类型：
--
作者：
Niu, Yawen;Zhao, Guiqiu;Xu, Qiang
目得：目的：探讨蛋白酶激活受体2（PAR-2）在烟曲霉感染角膜中的作用。用A.用PAR-2拮抗剂（FSLLRY-NH 2）预处理或不预处理烟曲霉。用75%乙醇灭活的A. FSLLRY-NH 2预处理或未预处理的烟曲霉。通过临床评分和裂隙灯照片记录疾病严重程度。PCR、Western印迹和ELISA检测PAR-2、IL-1 β、TNF-α、IFN-γ、MIP-2和p-ERK 1/2的表达。结果：A. FSLLRY-NH 2显著抑制小鼠角膜中的上调。与感染对照相比，FSLLRY-NH 2降低疾病反应、PMN浸润和促炎细胞因子表达。A. FSLLRY-NH 2对烟曲霉的生长有显著抑制作用。FSLLRY-NH 2可显著抑制感染细胞中促炎细胞因子蛋白的表达，其表达可能受到p-ERK 1/2的修饰。烟曲霉毒素增加PAR-2的表达，并通过PAR-2增加疾病、PMN浸润和促炎细胞因子表达，这可能被p-ERK 1/2修饰。
PURPOSE: To determine the role of protease-activated receptor-2 (PAR-2) in cornea infected by Aspergillus fumigatus.METHODS: PAR-2 was tested in normal and infected corneas of C57BL/6 mice. Mice corneas were infected with A. fumigatus with or without pretreatment of PAR-2 antagonist (FSLLRY-NH2). Polymorphonuclear neutrophilic leukocytes (PMNs) were stimulated with 75% ethanol-killed A. fumigatus with or without pretreatment of FSLLRY-NH2. Disease severity was documented by clinical score and photographs with a slit lamp. PCR, Western blot, and ELISA tested expression of PAR-2, IL-1 beta, TNF-alpha, IFN-gamma, MIP-2, and p-ERK1/2. PMN infiltration was assessed by myeloperoxidase assay and immunofluorescent staining.RESULTS: PAR-2 expression was significantly elevated by A. fumigatus, whereas the upregulation was significantly inhibited by FSLLRY-NH2 in mice corneas. FSLLRY-NH2 decreased disease response, PMN infiltration, and proinflammatory cytokine expression compared with infected control. In PMNs, PAR-2 expression was also significantly increased by A. fumigatus, which was significantly inhibited by FSLLRY-NH2. FSLLRY-NH2 significantly inhibited proinflammatory cytokine protein expression, as compared with that in infected control cells, which may be modified by p-ERK1/2.CONCLUSIONS: These data provide evidence that A. fumigatus increased PAR-2 expression and elevated disease, PMN infiltration, and proinflammatory cytokine expression through PAR-2, which may be modified by p-ERK1/2.