MCPIP1 alleviates inflammatory response through inducing autophagy in Aspergillus fumigatus keratitis

烟曲霉 自噬 真菌性角膜炎 免疫系统 微生物学 促炎细胞因子 角膜炎 基因敲除 炎症 免疫学 生物 细胞培养 细胞凋亡 生物化学 遗传学
作者
Fang Han,Lin Shen,Hanlin Ma,Leyi Wang,Hui Guo,Xinyi Wu
出处
期刊:International Immunopharmacology [Elsevier BV]
卷期号:113: 109279-109279 被引量:6
标识
DOI:10.1016/j.intimp.2022.109279
摘要

• A. fumigatus infection promotes MCPIP1 expression in HCECs and in mouse corneas. • MCPIP1 enhances autophagy flux by inhibiting the mTOR signaling in HCECs. • MCPIP1 inhibits inflammatory response by inducing autophagy in HCECs infected with A. fumigatus . • MCPIP1 alleviates the severity of keratitis by activating autophagy in an FK mouse model. Fungal keratitis (FK) is a serious corneal infection caused by pathogenic fungi. Monocyte chemoattractant protein-induced protein 1 (MCPIP1) plays an important role in restricting the inflammatory response in various immune disorders. However, the function of MCPIP1 in Aspergillus fumigatus ( A. fumigatus ) keratitis is unclear. In the present study, we found that A. fumigatus infection promotes the expression of MCPIP1 in human corneal epithelial cells (HCECs) and in mouse corneas. Overexpression of MCPIP1 decreased the production of inflammatory cytokines, including TNF-α, IL-6, and IL-1β, while knockdown of MCPIP1 increased the expression of these cytokines. MCPIP1 enhanced autophagy flux by inhibiting the mTOR signaling in HCECs with A. fumigatus infection. Further study showed that inhibition of autophagy using chloroquine reverses the anti-inflammatory effect of MCPIP1 in HCECs infected with A. fumigatus . Moreover, MCPIP1 alleviated the severity of keratitis and inhibited the expression of inflammatory cytokines by activating autophagy in an FK mouse model. In conclusion, our study demonstrated that MCPIP1 alleviates the severity of A. fumigatus keratitis by inducing mTOR-mediated autophagy in HCECs and in a mouse model. Exogenous use of MCPIP1 protein may have potential applications in FK clinical therapy.
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