Role of the IL-33/ST2/p38 signaling pathway in the immune response of corneal epithelial cells to Aspergillus fumigatus infection

• 作者: Cui Li Gui-Qiu Zhao Guo-Qiang Zhu Hong He Jia You Jing Lin Xu-Dong Peng Xue-Qi Zhao Yi-Fan Zhou
• 来源期刊: 国际眼科杂志:英文版
• 学科: 医学
• 关键词: ST2 interleukin 33 ASPERGILLUS FUMIGATUS CORNEA P38 MITOGEN-ACTIVATED protein kinase proliferation
• 年，卷（期）: 2019,（4）
• 页码范围: 549-556
• 页数: 8页
• 分类号: R

摘要

AIM: To investigate the expression of interleukin (IL)-33 in the cornea and human corneal epithelial cells (HCECs) exposed to Aspergillus fumigatus (A. fumigatus), and to determine the function of IL-33/ST2/p38 signaling pathway in the immune response of corneal epithelial cells to A. fumigatus infection. METHODS: The mRNA and protein expression of IL-33 in HCECs and mice corneas were examined by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis, respectively. IL-33 expression was also detected in cornea samples from healthy donors and patients with fungal keratitis with immunohistochemistry. The cultured HCECs were treated with inactive A. fumigatus hyphae at various concentrations with or without recombinant human IL-33 protein, soluble recombinant ST2 protein, specific ST2 neutralizing antibody, or the mitogen-activated protein kinase (MAPK) p38 inhibitor SB203580 for evaluation of the expression and activation of IL-33/ST2/p38 signaling in the regulation of proinflammatory cytokines. The production levels of IL-6 and IL-1β were determined by qRT-PCR and enzyme-linked immunosorbent assay (ELISA). The proliferation of HCECs was determined by a Cell Counting Kit-8 (CCK8) assay and cell count. RESULTS: IL-33 expression levels increased in the corneal tissues of patients with fungal keratitis and in mice corneas of experimental A. fumigatus infection, as well as in HCECs with infection of A. fumigatus. A. fumigatus strongly stimulated HCECs-generated proinflammatory cytokine (IL-6 and IL-1β) production at both the mRNA and protein levels. This production of pro-inflammatory mediators stimulated by A. fumigatus was further stimulated by IL-33 and was prevented by soluble ST2 protein or ST2 neutralizing antibody. Moreover, IL-33 naturally promoted the p38 phosphorylation induced by A. fumigatus, which was suppressed by soluble ST2 protein. The MAPK p38 inhibitor SB203580 also inhibited the A. fumigatus-induced proinflammatory cytokine production. IL-33 admin