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首页> 外文期刊>Cell biology international. >Inhibition of lipopolysaccharide-mediated rat alveolar macrophage activation in vitro by antiflammin-1.
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Inhibition of lipopolysaccharide-mediated rat alveolar macrophage activation in vitro by antiflammin-1.

机译:antiflammin-1在体外抑制脂多糖介导的大鼠肺泡巨噬细胞活化。

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Antiflammin-1 (AF-1) is a synthetic nonapeptide with a similar sequence to the conserved sequence of CC10 secreted by lung Clara cells. Studies suggest that it is potent inhibitor of inflammation. We investigated the effects and possible mechanisms of AF-1 on LPS-induced alveolar macrophage (AM) activation in vitro. AMs harvested from the BALF of Sprague-Dawley (SD) rat were treated with various concentrations of AF-1 both simultaneously and after LPS stimulation. The concentrations of the cytokines IL-1beta, IL-6, and IL-10 in the supernatant were detected by an enzyme-linked immunosorbent assay. The mRNA expression levels of these cytokines in AMs were analyzed using quantitative RT-PCR. To investigate more fully the possible mechanisms by which AF-1 modulates the expression of cytokines, cells were pretreated with anti-IL-10 antibody. Toll-like receptor-4 (TLR-4) expression on the cell surface was also detected using flow cytometry. The results showed that AF-1 suppressed mRNA expression and proteinproduction of IL-1beta and IL-6, while it promoted IL-10 expression in LPS-stimulated AMs, in a dose-dependent manner. The inhibitory effects of AF-1 on IL-1beta were significantly decreased when endogenous production of IL-10 was blocked. AF-1 also showed an effect on downregulated TLR-4 expression in LPS-stimulated AMs. The data show for the first time that AF-1 modulates the AM response to LPS by regulating TLR-4 expression and upregulating IL-10 secretion, which could be another important mechanism in the AF-1 inhibiting effect on inflammation.
机译:Antiflammin-1(AF-1)是一种合成的九肽,其序列与肺克拉拉细胞分泌的CC10保守序列相似。研究表明,它是有效的炎症抑制剂。我们调查了AF-1对LPS诱导的肺泡巨噬细胞(AM)体外激活的影响和可能的机制。同时和在LPS刺激之后,用各种浓度的AF-1处理从Sprague-Dawley(SD)大鼠的BALF中收获的AM。通过酶联免疫吸附测定法检测上清液中细胞因子IL-1β,IL-6和IL-10的浓度。使用定量RT-PCR分析这些细胞因子在AM中的mRNA表达水平。为了更全面地研究AF-1调节细胞因子表达的可能机制,将细胞用抗IL-10抗体进行了预处理。还使用流式细胞仪检测了细胞表面Toll样受体4(TLR-4)的表达。结果表明,AF-1以剂量依赖的方式抑制LPS刺激的AMs中IL-1beta和IL-6的mRNA表达和蛋白质生成,同时促进IL-10的表达。阻断内源性IL-10产生后,AF-1对IL-1beta的抑制作用明显降低。 AF-1还显示了对LPS刺激的AMs中TLR-4表达下调的作用。数据首次显示AF-1通过调节TLR-4表达和上调IL-10分泌来调节AM对LPS的反应,这可能是AF-1抑制炎症的另一重要机制。

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