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首页> 外文期刊>Clinical and Experimental Immunology: An Official Journal of the British Society for Immunology >Circulating IgA from acute stage of childhood Henoch-Schonlein purpura can enhance endothelial interleukin (IL)-8 production through MEK/ERK signalling pathway.
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Circulating IgA from acute stage of childhood Henoch-Schonlein purpura can enhance endothelial interleukin (IL)-8 production through MEK/ERK signalling pathway.

机译:从儿童过敏性紫癜急性期开始循环IgA可通过MEK / ERK信号通路增强内皮白细胞介素(IL)-8的产生。

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摘要

Recently, sera from children with active Henoch-Schonlein purpura (HSP) have been found to enhance interleukin (IL)-8 production by human umbilical venous endothelial cells (HUVEC). To further determine the possible factor with the ability to enhance endothelial IL-8 production in sera from acute stage of HSP, 10 children with HSP at the acute stage and 10 healthy controls were enrolled. IgA antiendothelial cell antibodies (AECA) were detected by cell-based ELISA. Active sera with or without pretreatment with anti-human IgA antibody, sera of controls, and immunoglobulin A (IgA) derived from sera were used to stimulate the HUVEC. The ability of these factors to enhance endothelial IL-8 production was evaluated. Furthermore, signalling pathways were also assayed by different inhibitors, and confirmed by immunoblotting. Serum levels of IgA AECA in HPS patients at the acute stage were significantly higher than in controls (P < 0.001). The active sera could enhance endothelial IL-8 production (P = 0.004, compared with control sera), and the ability of these sera was mostly abolished when pretreated with fixed anti-human IgA antibody. The supernatant IL-8 levels of endothelial cells stimulated by IgA derived from acute stage of HSP were statistically higher than controls (P < 0.001). PD98059, an inhibitor of ERK phosphorylation, significantly reduced IgA AECA-stimulated endothelial IL-8. IgA AECA also enhanced the phosphorylation of ERK1 with a time-dependent manner. Together with these findings, it is concluded that IgA AECA derived from acute stage of HSP may bind to endothelial and enhance endothelial cells to produce IL-8 via MEK/REK signalling pathway.
机译:最近,发现患有活动性过敏性紫癜(HSP)儿童的血清可增强人脐静脉内皮细胞(HUVEC)产生的白介素(IL)-8。为了进一步确定可能增强HSP急性期血清中内皮IL-8产生能力的因素,招募了10例急性期HSP儿童和10名健康对照。通过基于细胞的ELISA检测IgA抗内皮细胞抗体(AECA)。用或不用抗人IgA抗体预处理的活性血清,对照血清和源自血清的免疫球蛋白A(IgA)用于刺激HUVEC。评价了这些因素增强内皮IL-8产生的能力。此外,还可以通过不同的抑制剂来分析信号通路,并通过免疫印迹进行确认。急性期HPS患者的血清IgA AECA水平显着高于对照组(P <0.001)。活性血清可以增强内皮细胞IL-8的产生(与对照血清相比,P = 0.004),并且在用固定的抗人IgA抗体进行预处理时,这些血清的能力大部分消失了。从HSP急性期获得的IgA刺激的内皮细胞上清液IL-8水平在统计学上高于对照组(P <0.001)。 PD98059是ERK磷酸化的抑制剂,可显着降低IgA AECA刺激的内皮细胞IL-8。 IgA AECA还以时间依赖性方式增强ERK1的磷酸化。结合这些发现,可以得出结论,源自HSP急性期的IgA AECA可能与内皮结合,并通过MEK / REK信号通路增强内皮细胞产生IL-8。

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