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首页> 外文期刊>Cytokine >Wheat gliadin promotes the interleukin-4-induced IgE production by normal human peripheral mononuclear cells through a redox-dependent mechanism.
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Wheat gliadin promotes the interleukin-4-induced IgE production by normal human peripheral mononuclear cells through a redox-dependent mechanism.

机译:小麦麦醇溶蛋白通过氧化还原依赖性机制促进正常人外周单核细胞白介素4诱导的IgE产生。

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Increased levels of serum IgE have been described in gliadin-intolerant patients; however, biological mechanisms implicated in this immunoglobulin production remained unknown. In this study, we demonstrated that in vitro crude gliadins and gliadin lysates (Glilys) promoted the IL-4-induced IgE production by human peripheral blood mononuclear cells (PBMC), indicating that the biological process related to gliadin intolerance and/or allergy may lead to IgE production in vivo. It was found that crude gliadin and Glilys potentiated, after 13 days of culture in a dose-dependent manner, IL-4-induced IgE production and, to a lesser extent, the IgG production, while they did not affect IgA or IgM productions. This promoting effect of gliadin and Glilys on the IL-4-induced activation of normal human PBMC was also observed on the early release (2 days) of the soluble fraction of CD23, suggesting its possible involvement in IgE potentiation. The promoting effect of crude gliadin and Glilys appeared to be indirectbecause they did not modify purified B-lymphocytes IgE production after IL-4 and anti-CD40 monoclonal antibody stimulation.In addition, as revealed by luminol-dependent chemiluminescence, we demonstrated that crude gliadin and Glilys promoted a substantial production of free radicals by normal human PBMC, treated or not with IL-4. This redox imbalance associated with an increased IgE production led us to evaluate the effect of pharmacological antioxidants (N-acetyl-cysteine (NAC) and Cu/Zn-superoxide dismutase (SOD1)) on IgE production by human PBMC. The NAC and the intracellularly delivered SOD1 were found to suppress the IL-4+/-crude gliadin or Glilys-induced IgE production by normal human PBMC. Taken together, these data indicated that gliadin specifically enhanced IL-4-induced IgE production by normal human PBMC, probably by the regulation of redox pathways, and that this 'pro-allergenic' effect could be counteracted by natural antioxidants: thiols and/or vectorized SOD1.
机译:已经描述了在不接受麦醇溶蛋白的患者中血清IgE水平升高;然而,涉及这种免疫球蛋白生产的生物学机制仍然未知。在这项研究中,我们证明了体外粗麦醇溶蛋白和麦醇溶蛋白裂解物(Glilys)促进了人外周血单核细胞(PBMC)产生的IL-4诱导的IgE生成,表明与麦醇溶蛋白不耐受和/或过敏有关的生物学过程可能导致体内产生IgE。发现在以剂量依赖性方式培养13天后,粗麦醇溶蛋白和Glilys增强了IL-4诱导的IgE产生,并在较小程度上增强了IgG产生,尽管它们不影响IgA或IgM产生。在CD23可溶性部分的早期释放(2天)中也观察到了麦醇溶蛋白和Glilys对IL-4诱导的正常人PBMC活化的促进作用,表明其可能参与了IgE增强。粗麦醇溶蛋白和Glilys的促进作用似乎是间接的,因为它们没有改变IL-4和抗CD40单克隆抗体刺激后纯化的B淋巴细胞IgE的产生。此外,如鲁米诺依赖性化学发光所揭示的,我们证明了粗麦醇溶蛋白Glilys促进了正常人PBMC大量产生自由基,无论是否用IL-4处理。与IgE产生增加相关的氧化还原失衡使我们评估了药理抗氧化剂(N-乙酰半胱氨酸(NAC)和Cu / Zn超氧化物歧化酶(SOD1))对人PBMC产生IgE的影响。发现NAC和细胞内递送的SOD1抑制正常人PBMC的IL-4 +/-粗麦醇溶蛋白或Glilys诱导的IgE产生。综上所述,这些数据表明麦醇溶蛋白可以通过正常的人PBMC特异性增强IL-4诱导的IgE产生,可能是通过氧化还原途径的调节,并且这种“促变应原性”作用可以被天然抗氧化剂抵消:硫醇和/或向量化SOD1。

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