毛状样蛋白敲除对过敏性哮喘的影响
首发时间:2020-02-14
摘要:毛状样蛋白(CLP)是一种纤维状肌动蛋白结合蛋白,还可以充当5-脂氧合酶(5LO)的支架。先前研究已经证明抑制CLP能够抑制5LO的活性,进而调节白三烯(LTs)的形成。但是,CLP如何影响过敏性哮喘的免疫反应尚不清楚。本研究通过生成CLP缺陷小鼠模型来解决此问题。结果表明,与野生型哮喘小鼠相比,CLP缺陷小鼠患有更严重的哮喘,表现为支气管肺泡灌洗液(BAL)免疫细胞浸润加剧,并且Th2型炎症因子升高。组织形态学分析表明,CLP缺陷哮喘小鼠的支气管收缩更为严重,并且呼吸道上皮的粘蛋白分泌更多。对BAL中的脂质分析结果证明了CLP对类二十烷酸的调控能力。通过对与类二十烷酸相关的蛋白酶和受体的分析,也表明CLP缺乏会导致哮喘小鼠前列腺素D2(PGD2)合成酶(HPGDS)和受体(CRTH2)上调。总之,本研究表明了CLP缺乏会导致小鼠哮喘恶化,并且这种恶化与PGD2是相关的。
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The effects of coactosin-like protein knockout on allergic asthma
Abstract:Coactosin-like protein (CLP) is an F-actin-binding protein that can also function as a scaffold for 5-lipoxygenase (5LO). A role for CLP in regulating 5LO and leukotriene (LT) formation has been described previously. However, how CLP might influence the immune response in allergic asthma is unknown. We approached this question by generating a CLP deficient mouse model. The results showed that clp-deficient mice had more immune cell infiltration in bronchoalveolar lavage (BAL) and higher levels of Th2 inflammatory cytokines after asthma than wild-type asthma mice. Histomorphological analysis showed that the bronchial contraction was more severe and mucin was more secreted in the respiratory epithelium of clp-deficient asthma mice. The results of lipid analysis in BAL proved the regulation ability of CLP to eicosanoids. Analysis of proteases and receptors associated with eicosanoids also showed that CLP deficiency led to up-regulation of prostaglanin D2 (PGD2) synthase (HPGDS) and receptor (CRTH2) in asthmatic mice. In summary, this study shows that lack of CLP leads to worsening of asthma in mice, and this deterioration is associated with PGD2.
Keywords: allergic asthma, coactosin-like protein, eicosanoids, prostaglandin
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