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Boswellic acid attenuates asthma phenotypes by downregulation of GATA3 via pSTAT6 inhibition in a murine model of asthma

机译:在哮喘小鼠模型中乳香酸通过抑制pSTAT6抑制GATA3的表达从而减轻哮喘的表型。

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摘要

Asthma is a serious global health problem characterised by airway inflammation, airway epithelial wall shedding, enhanced mucus production, increased IgE levels and airway hyperresponsiveness. The pathophysiology of asthma is mediated by Th2 cells which produce Th2 cytokines like interleukin-4, interleukin-5, interleukin-13 and interleukin-9. The differentiation of Th2 cells is induced by the transcription factor GATA3 which is activated by pSTAT6 via IL-4 signalling. To investigate the anti-asthmatic potential of Boswellic acid, as well as the underlying mechanism involved, we studied its anti-asthmatic potential in a murine model of asthma. In this study, BALB/c mice were systemically sensitized by ovalbumin (OVA) followed by aerosol allergen challenges. We investigated the effect of Boswellic acid on airway hyperresponsiveness, inflammatory cell infiltration, Th2 cytokine and OVA-specific IgE production in a mouse model of asthma. We found that Boswellic acid treated groups suppressed allergic airway inflammation, AHR, OVA-specific IgE and Th2 cytokines secretion. It also suppressed the expression of pSTAT6 and GATA3 in a dose dependent manner. Our data suggest that the mechanism by which Boswellic acid effectively treats asthma is based on reductions of Th2 cytokines via inhibition of pSTAT6 and GATA-3 expression.
机译:哮喘是一个严重的全球性健康问题,其特征是气道炎症,气道上皮壁脱落,粘液产生增加,IgE水平升高和气道高反应性。哮喘的病理生理是由Th2细胞介导的,Th2细胞产生Th2细胞因子,如白介素4,白介素5,白介素13和白介素9。 Th2细胞的分化是由转录因子GATA3诱导的,该转录因子被pSTAT6经由IL-4信号激活。为了研究乳香酸的抗哮喘潜力及其涉及的潜在机制,我们研究了其在哮喘小鼠模型中的抗哮喘潜力。在这项研究中,卵清蛋白(OVA)对BALB / c小鼠进行全身致敏,然后进行气溶胶过敏原攻击。我们在哮喘小鼠模型中研究了乳香酸对气道高反应性,炎性细胞浸润,Th2细胞因子和OVA特异性IgE产生的影响。我们发现,乳香酸治疗组抑制了过敏性气道炎症,AHR,OVA特异性IgE和Th2细胞因子的分泌。它还以剂量依赖性的方式抑制了pSTAT6和GATA3的表达。我们的数据表明,乳香酸有效治疗哮喘的机制基于通过抑制pSTAT6和GATA-3表达而减少Th2细胞因子。

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