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Dehydroxymethylepoxyquinomicin (DHMEQ), a novel NF-kappaB inhibitor, inhibits allergic inflammation and airway remodelling in murine models of asthma

机译：新型的NF-κB抑制剂Dehydroxymethylepoxyquinomicnomicin（DHMEQ）抑制哮喘小鼠模型中的过敏性炎症和气道重塑

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Summary: Background: Dehydroxymethylepoxyquinomicin (DHMEQ) is a newly developed compound that inhibits nuclear factor κB activation and is reported to ameliorate animal models of various inflammatory diseases without significant adverse effects. Because nuclear factor κB is a transcription factor that plays a critical role in the pathophysiology of asthma, DHMEQ may be of therapeutic benefit in asthma. Objective: The purpose of this study was to evaluate the effects of DHMEQ on airway inflammation and remodelling in murine models of asthma. Methods: The BALB/c mice were sensitized and then challenged acutely or chronically with ovalbumin and administered DHMEQ intraperitoneally before each challenge. Inflammation of airways, lung histopathology and airway hyper responsiveness to methacholine challenge were evaluated. In addition, the effect of DHMEQ on production of cytokines and eotaxin-1 by murine splenocytes, human peripheral blood mononuclear cells and bronchial epithelial cells was investigated. Results: Airway hyper responsiveness was ameliorated in both acutely and chronically challenged models by treatment with DHMEQ. DHMEQ significantly reduced eosinophilic airway inflammation and levels of Th2 cytokines in bronchoalveolar lavage fluid in the acute model. It also inhibited parameters of airway remodelling including mucus production, peribronchial fibrosis and the expression of α-smooth muscle actin. Moreover, the production of Th2 cytokines from murine splenocytes and human peripheral blood mononuclear cells and the production of eotaxin-1 by bronchial epithelial cells were inhibited by DHMEQ. Conclusions and Clinical Relevance: These results indicate that DHMEQ inhibits allergic airway inflammation and airway remodelling in murine models of asthma. DHMEQ may have therapeutic potential in the treatment of asthma.
机译：摘要：背景：脱羟甲基环氧喹诺酮（DHMEQ）是一种新开发的化合物，可抑制核因子κB活化，据报道可改善各种炎症性疾病的动物模型，而没有明显的不良影响。因为核因子κB是在哮喘的病理生理中起关键作用的转录因子，所以DHMEQ可能对哮喘有治疗作用。目的：本研究旨在评估DHMEQ对哮喘小鼠模型中气道炎症和重塑的影响。方法：将BALB / c小鼠致敏，然后用卵清蛋白急性或慢性激发，并在每次激发前腹膜内给予DHMEQ。评估气道炎症，肺组织病理学和气道对乙酰甲胆碱激发的高反应性。此外，研究了DHMEQ对鼠脾细胞，人外周血单核细胞和支气管上皮细胞产生细胞因子和eotaxin-1的影响。结果：通过DHMEQ治疗，急性和慢性挑战模型中的气道高反应性得到改善。在急性模型中，DHMEQ显着降低了嗜酸性细胞的气道炎症和支气管肺泡灌洗液中Th2细胞因子的水平。它还抑制气道重塑的参数，包括粘液产生，支气管周纤维化和α-平滑肌肌动蛋白的表达。此外，DHMEQ抑制了小鼠脾细胞和人外周血单核细胞中Th2细胞因子的产生以及支气管上皮细胞中eotaxin-1的产生。结论和临床意义：这些结果表明DHMEQ在哮喘小鼠模型中抑制了过敏性气道炎症和气道重塑。 DHMEQ在哮喘的治疗中可能具有治疗潜力。

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