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Camostat mesilate inhibits pro- inflammatory cytokine secretion and improves cell viability by regulating MFGE8 and HMGN1 in lipopolysaccharide- stimulated DF-1 chicken embryo fibroblasts

文献类型： 外文期刊

作者： Yuan, Lin 1 ; Li, Mengjie 2 ; Zhang, Zhishuai 3 ; Li, Wanli 1 ; Jin, Wei 1 ; Wang, Mingfa 1 ;

作者机构： 1.Henan Acad Agr Sci, Inst Anim Husb & Vet Med, Henan Key Lab Farm Anim Breeding & Nutr Regulat, Zhengzhou, Henan, Peoples R China

2.Bur Agr & Rural Affairs Longting Dist, Kaifeng, Henan, Peoples R China

3.Henan Inst Anim Hlth Supervis, Zhengzhou, Henan, Peoples R China

关键词： Camostat mesilate; Lipopolysaccharide; Fibroblast; Chicken; Inflammation; Viability; Apoptosis; MFGE8

期刊名称：PEERJ （ 影响因子：2.984； 五年影响因子：3.369 ）

ISSN： 2167-8359

年卷期： 2021 年 9 卷

页码：

收录情况： SCI

摘要： Camostat mesilate (CM) possesses potential anti-viral and anti-inflammatory activities. However, it remains unknown whether CM is involved in lipopolysaccharide (LPS)-mediated inflammatory responses and cell injury. In this project, differentially expressed proteins (DEPs, fold change >= 1.2 or < 0.83 and Q value < 0.05) in response to LPS stimulation alone or in combination with CM were identified through tandem mass tags (TMT)/mass spectrometry (MS)-based proteomics analysis in DF-1 chicken embryo fibroblasts. The mRNA expression levels of filtered genes were determined by RT-qPCR assay. The results showed that CM alleviated the detrimental effect of LPS on cell viability and inhibited LPS-induced TNF-alpha and IL-6 secretions in DF-1 chicken embryo fibroblasts. A total of 141 DEPs that might be involved in mediating functions of both LPS and CM were identified by proteomics analysis in DF-1 chicken embryo fibroblasts. LPS inhibited milk fat globule EGF and factor V/VIII domain containing (MFGE8) expression and induced high mobility group nucleosome binding domain 1 (HMGN1) expression, while these effects were abrogated by CM in DF-1 chicken embryo fibroblasts. MFGE8 knockdown facilitated TNF-alpha and IL-6 secretions , reduced cell viability, stimulated cell apoptosis in DF-1 chicken embryo fibroblasts co-treated with LPS and CM. HMGN1 loss did not influence TNF-alpha and IL-6 secretions, cell viability, and cell apoptosis in DF-1 chicken embryo fibroblasts co-treated with LPS and CM. In conclusion, CM exerted anti-inflammatory and pro-survival activities by regulating MFGE8 in LPS-stimulated DF-1 chicken embryo fibroblasts, deepening our understanding of the roles and molecular basis of CM in protecting against Gramnegative bacteria.

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