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首页> 外文期刊>The FASEB Journal >Leukotriene B4 receptor BLT2 negatively regulates allergic airway eosinophilia
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Leukotriene B4 receptor BLT2 negatively regulates allergic airway eosinophilia

机译:白酮B4受体BLT2负调节过敏气道嗜酸性粒细胞

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Leukotriene B4 (LTB4) has been implicated in the pathogenesis of allergic diseases. BLT2, a low-affinity LTB4 receptor, is activated by LTB4 and 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT). Although the high-affinity LTB4 receptor BLT1 has been shown to exert proinflammatory roles, the role of BLT2 in allergic inflammation has not been clarified. To study the function of BLT2 in development of asthma, we used mice model of ovalbumin (OVA)-induced allergic airway disease. The 12-HHT levels were elevated in bronchoalveolar lavage (BAL) fluids of OVA-sensitized/challenged wild-type mice. BLT2-deficient mice exhibited enhanced eosinophilia in BAL fluids after OVA exposure. Interleukin (IL)-13 levels in BAL fluids and IL-13-producing CD4+ T cells in the lungs were elevated in BLT2-deficient mice compared to wild-type mice, whereas the levels of IL-4, IL-5, and interferon (IFN)-γ in BAL fluids and serum OVA-specific IgE were comparable. Transfection of BLT2-specific small interfering RNA enhanced IL-13 production in CD4+ T cells in vitro. Expression of BLT2 mRNA in CD4+ T cells was significantly reduced in patients with asthma compared to healthy control subjects. These findings indicate that BLT2 has a protective role in allergic airway inflammation and that diminished BLT2 expression in CD4+ T cells may contribute to the pathophysiology of asthma.—Matsunaga, Y., Fukuyama, S., Okuno, T., Sasaki, F., Matsunobu, T., Asai, Y., Matsumoto, K., Saeki, K., Oike, M., Sadamura, Y., Machida, K., Nakanishi, Y., Kubo, M., Yokomizo, T., Inoue, H. Leukotriene B4 receptor BLT2 negatively regulates allergic airway eosinophilia.
机译:白三烯B4(LTB4)涉及过敏性疾病的发病机制。 BLT2,低亲和力LTB4受体由LTB4和12(S) - 羟基庚酰基-5Z,8E,10E-三烯酸(12-HHT)活化。尽管已经显示出高亲和力LTB4受体BLT1施加促炎作用,但是BLT2在过敏性炎症中的作用尚未阐明。为了研究BLT2在哮喘发展中的功能,我们使用了卵烧(OVA)诱导的过敏气道疾病的小鼠模型。 12-HHT水平升高于卵巢敏化/挑战野生型小鼠的支气管肺泡灌洗液(BAL)液体。在OVA暴露后,BLT2缺陷小鼠在BAL流体中表现出增强的嗜酸性粒细胞虫。与野生型小鼠相比,在BLT2缺陷小鼠中升高了肺中的BAL流体和IL-13的CD4 + T细胞的白细胞介素(IL)-13水平,而IL-4,IL-5和干扰素的水平升高(IFN)-γ在BAL流体和血清OVA特异性IgE相当。在体外转染BLT2特异性小干扰RNA增强的IL-13在CD4 + T细胞中产生。与健康对照对象哮喘患者,CD4 + T细胞中BLT2 mRNA在CD4 + T细胞中的表达显着降低。这些发现表明,BLT2在过敏气道炎症中具有保护作用,并且CD4 + T细胞中的BLT2表达减少可能有助于哮喘的病理生理学。-Matsunaga,Y.,Fukuyama,S.,Okuno,T.,Sasaki,F。 ,Matsunobu,T.,Asai,Y.,Matsumoto,K.,Saeki,K.,Oike,M.,Sadamura,Y.,Machida,K.,Nakanishi,Y.,Kubo,M.,Yokomizo,T. ,inoue,H.白酮二烯B4受体Blt2负调节过敏气道嗜酸性粒细胞。

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