Inhibitory Effects of Antimicrobial Peptide JH-3 on Salmonella enterica Serovar Typhimurium Strain CVCC541 Infection-Induced Inflammatory Cytokine Release and Apoptosis in RAW264.7 Cells

Molecules

Wanhai Qin¹  Gaiping Zhang²  Shijun Chen³  Chunling Zhu³  Huihui Zhang³  Yanzhao Xu³  Yawei Sun³  Xueqin Zhao³  Bolin Hang³  Lei Wang³  Jinqing Jiang³  Xiaojing Xia³  Jianhe Hu³ 

[1] Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, 1000 Amsterdam, The Netherlands;College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450000, China;College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang 453003, China;

关键词: antimicrobial peptide JH-3;    apoptosis;    cytokines;    Salmonella;   

DOI  :  10.3390/molecules24030596

来源: DOAJ

【 摘 要 】

The antibiotic resistance of Salmonella has become increasingly serious due to the increased use of antibiotics, and antimicrobial peptides have been considered as an ideal antibiotic alternative. Salmonella can induce macrophage apoptosis and thus further damage the immune system. The antimicrobial peptide JH-3 has been shown to have a satisfactory anti-Salmonella effect in previous research, but its mechanism of action remains unknown. In this study, the effects of JH-3 on macrophages infected with Salmonella Typhimurium CVCC541 were evaluated at the cellular level. The results showed that JH-3 significantly alleviated the damage to macrophages caused by S. Typhi infection, reduced the release of lactic dehydrogenase (LDH), and killed the bacteria in macrophages. In addition, JH-3 decreased the phosphorylation level of p65 and the expression and secretion of interleukin 2 (IL-2), IL-6, and tumor necrosis factor-α (TNF-α) by inhibiting the activation of the mitogen-activated protein kinase (MAPK) (p38) signaling pathway and alleviating the cellular inflammatory response. From confocal laser scanning microscopy and flow cytometry assays, JH-3 was observed to inhibit the release of cytochrome c in the cytoplasm; the expression of TNF-αR2, caspase-9, and caspase-8; to further weaken caspase-3 activation; and to reduce the S.-Typhi-induced apoptosis of macrophages. In summary, the mechanism by which JH-3 inhibits Salmonella infection was systematically explored at the cellular level, laying the foundation for the development and utilization of JH-3 as a therapeutic alternative to antibiotics.

【 授权许可】

Unknown