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Interferon-gamma enhances both the anti-bacterial and the pro-inflammatory response of human mast cells to Staphylococcus aureus

机译:γ-干扰素增强人肥大细胞对金黄色葡萄球菌的抗菌和促炎反应

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摘要

Human mast cells (huMCs) are involved in both innate and adaptive immune responses where they release mediators including amines, reactive oxygen species (ROS), eicosanoids and cytokines. We have reported that interferon- (IFN-gamma) enhances FcR-dependent ROS production. The aim of this study was to extend these observations by investigating the effect of IFN- on the biological responses of huMCs to Staphylococcus aureus. We found that exposure of huMCs to S.aureus generated intracellular and extracellular ROS, which were enhanced in the presence of IFN-gamma IFN-gamma also promoted bacteria killing, -hexosaminidase release and eicosanoid production. Interferon- similarly increased expression of mRNAs encoding CCL1 to CCL4, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor- and CXCL8 in S.aureus-stimulated huMCs. The ability of IFN- to increase CXCL8 and GM-CSF protein levels was confirmed by ELISA. Fibronectin or a beta(1) integrin blocking antibody completely abrogated IFN-gamma-dependent S.aureus binding and reduced S.aureus-dependent CXCL8 secretion. These data demonstrate that IFN-gamma primes huMCs for enhanced anti-bacterial and pro-inflammatory responses to S.aureus, partially mediated by beta(1) integrin.
机译:人类肥大细胞(huMC)参与先天性和适应性免疫反应,它们释放包括胺,活性氧(ROS),类花生酸和细胞因子在内的介体。我们已经报道了干扰素(IFN-γ)增强了FcR依赖性ROS的产生。这项研究的目的是通过研究IFN-对huMC对金黄色葡萄球菌的生物学反应的影响来扩展这些观察结果。我们发现huMCs暴露于金黄色葡萄球菌会产生细胞内和细胞外ROS,在IFN-γ的存在下它们会增强,而IFN-γ也会促进细菌杀伤,-己糖胺酶的释放和类花生酸的产生。在金黄色葡萄球菌刺激的huMC中,干扰素类似地增加了编码CCL1到CCL4,粒细胞巨噬细胞集落刺激因子(GM-CSF),肿瘤坏死因子和CXCL8的mRNA的表达。 ELISA证实了IFN-增加CXCL8和GM-CSF蛋白水平的能力。纤连蛋白或beta(1)整合素阻断抗体完全废除了IFN-γ依赖性金黄色葡萄球菌的结合并减少了金黄色葡萄球菌依赖性CXCL8的分泌。这些数据表明,IFN-γ引发huMC增强对金黄色葡萄球菌的抗菌和促炎反应,部分由β(1)整合素介导。

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