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Immunomodulatory gene expression analysis in LPS-stimulated human polymorphonuclear leukocytes treated with antibiotics commonly used for multidrug-resistant strains
Molecular Immunology ( IF 3.2 ) Pub Date : 2020-11-30 , DOI: 10.1016/j.molimm.2020.11.012
Tsuneyuki Ubagai , Yoshinori Sato , Go Kamoshida , Yuka Unno , Yasuo Ono

Conventional antibiotics used for the treatment of severe infections such as sepsis and septic shock confer immunomodulatory benefits. However, the growing problem of multidrug resistant infections has led to an increase in the administration of non-conventional last-resort antibiotics, including quinolones, aminoglycosides, and polypeptides, and the effects of these drugs on immunomodulatory gene expression in activated human polymorphonuclear leukocytes (PMNs) have not been reported. In this study, lipopolysaccharide-stimulated PMNs were incubated with piperacillin, rifampicin, fosfomycin (FOM), levofloxacin (LVFX), minocycline (MINO), colistin, tigecycline, or amikacin, and the mRNA expression levels of pattern recognition receptors (TLR2, TLR4, and CD14), inflammatory cytokines (TNFα and IL6), and chemokine receptors (IL8Rs and ITGAM) in these cells were quantitated using real-time qPCR. Many of the tested antibiotics altered the expression of the investigated cytokines. Notably, FOM, LVFX, and MINO significantly downregulated the expression of IL6, which is associated with pro- and anti-inflammatory defense mechanisms. Treatment of FOM and LVFX reduced IL-6 production as well as observed for IL6 gene expression. These findings indicated transcription and translation cooperation under the used experimental conditions. Therefore, our findings suggest that administration of these antibiotics suppresses the host anti-inflammatory response.



中文翻译:

用多药耐药菌株常用抗生素处理LPS刺激的人多形核白细胞中的免疫调节基因表达分析

用于治疗严重感染如败血症和败血性休克的常规抗生素具有免疫调节作用。然而,日益增长的多药耐药性感染问题导致非常规最后使用的抗生素(包括喹诺酮类,氨基糖苷类和多肽类)的施用增加,以及这些药物对活化的人多形核白细胞中免疫调节基因表达的影响(尚未报告PMN)。在这项研究中,将脂多糖刺激的PMN与哌拉西林,利福平,磷霉素(FOM),左氧氟沙星(LVFX),米诺环素(MINO),粘菌素,替加环素或丁胺卡那霉素以及模式识别受体的mRNA表达水平(TLR2,TLR4CD14),炎性细胞因子(使用实时定量PCR定量这些细胞中的TNFαIL6以及趋化因子受体(IL8RITGAM)。许多测试的抗生素改变了所研究的细胞因子的表达。值得注意的是,FOM,LVFX和MINO显着下调了IL6的表达,这与促炎和抗炎防御机制有关。FOM和LVFX的治疗降低了IL-6的产生,并观察到了IL6基因的表达。这些发现表明在所用实验条件下的转录和翻译合作。因此,我们的发现表明,这些抗生素的施用抑制了宿主的抗炎反应。

更新日期:2020-12-01
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