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
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
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抗菌肽JH-3对肠沙门氏菌鼠伤寒血清型CVCC541感染诱导的RAW264.7细胞炎症细胞因子释放和凋亡的抑制作用
DOI：
10.3390/molecules24030596
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发表时间：
2019-02-01
期刊：
影响因子：
4.6
通讯作者：
Hu，Jianhe
中科院分区：
文献类型：
--
作者：
Wang，Lei;Zhao，Xueqin;Hu，Jianhe
随着抗生素使用的增加，沙门氏菌的耐药性日益严重，抗菌肽被认为是理想的抗生素替代品。沙门氏菌可诱导巨噬细胞凋亡，从而进一步损害免疫系统。抗菌肽JH-3具有良好的抗沙门氏菌作用，但其作用机制尚不清楚。本研究在细胞水平上观察JH-3对鼠伤寒沙门氏菌CVCC 541感染巨噬细胞的影响。结果表明，JH-3能明显减轻S.伤寒杆菌感染后，乳酸脱氢酶（LDH）的释放减少，并杀死了巨噬细胞中的细菌。此外，JH-3还通过抑制丝裂原活化蛋白激酶（MAPK）（p38）信号通路的活化，减轻细胞炎症反应，从而降低p65的磷酸化水平，抑制白细胞介素2（IL-2）、IL-6和肿瘤坏死因子-α（TNF-α）的表达和分泌。通过激光共聚焦显微镜和流式细胞仪分析，观察到JH-3抑制细胞质中细胞色素c的释放; TNF-αR2、caspase-9和caspase-8的表达;进一步减弱caspase-3的激活;并减少S.伤寒杆菌诱导的巨噬细胞凋亡。综上所述，本文在细胞水平上系统地探讨了JH-3抑制沙门氏菌感染的机制，为JH-3作为抗生素替代治疗药物的开发和利用奠定了基础。
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.