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MAG-EPA resolves lung inflammation in an allergic model of asthma

机译：MAG-EPA解决哮喘过敏模型中的肺部炎症

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Background: Asthma is a chronic disease characterized by airways hyperresponsiveness, inflammation and airways remodelling involving reversible bronchial obstruction. Omega-3 fatty acids and their derivatives are known to reduce inflammation in several tissues including lung. Objectives: The effects of eicosapentaenoic acid monoacylglyceride (MAG-EPA), a newly synthesized EPA derivative, were determined on the resolution of lung inflammation and airway hyperresponsiveness in an in vivo model of allergic asthma. Methods: Ovalbumin (OVA)-sensitized guinea-pigs were treated or not with MAG-EPA administered per os. Isometric tension measurements, histological analyses, homogenate preparation for Western blot experiments or total RNA extraction for RT-PCR were performed to assess the effect of MAG-EPA treatments. Results: Mechanical tension measurements revealed that oral MAG-EPA treatments reduced methacholine (MCh)-induced bronchial hyperresponsiveness in OVA-sensitized guinea-pigs. Moreover, MAG-EPA treatments also decreased Ca2+ hypersensitivity of bronchial smooth muscle. Histological analyses and leucocyte counts in bronchoalveolar lavages revealed that oral MAG-EPA treatments led to less inflammatory cell recruitment in the lung of OVA-sensitized guinea-pigs when compared with lungs from control animals. Results also revealed a reduction in mucin production and MUC5AC expression level in OVA-sensitized animals treated with MAG-EPA. Following MAG-EPA treatments, the transcript levels of pro-inflammatory markers such as IL-5, eotaxin, IL-13 and IL-4 were markedly reduced. Moreover, per os MAG-EPA administrations reduced COX2 over-expression in OVA-sensitized animals. Conclusion and Clinical Relevance: We demonstrate that MAG-EPA reduces airway hyperresponsiveness and lung inflammation in OVA-sensitized animals, a finding consistent with a decrease in IL-4, IL-5, IL-13, COX-2 and MUC5AC expression levels in the lung. The present data suggest that MAG-EPA represents a new potential therapeutic strategy for resolving inflammation in allergic asthma.
机译：背景：哮喘是一种慢性疾病，其特征在于气道反应过度，炎症和涉及可逆性支气管阻塞的气道重塑。已知Omega-3脂肪酸及其衍生物可减轻包括肺在内的多种组织的炎症。目的：确定过敏性哮喘体内模型中新合成的EPA衍生物二十碳五烯酸单酰基甘油酯（MAG-EPA）对肺部炎症和气道高反应性的缓解作用。方法：是否经口服MAG-EPA来治疗卵清蛋白（OVA）致敏的豚鼠。进行了等轴测张力测量，组织学分析，Western印迹实验的匀浆制备或RT-PCR的总RNA提取，以评估MAG-EPA处理的效果。结果：机械张力测量结果表明，口服MAG-EPA处理可降低甲酰胆碱（MCh）在OVA致敏的豚鼠中引起的支气管高反应性。此外，MAG-EPA治疗还降低了支气管平滑肌的Ca2 +超敏性。组织学分析和支气管肺泡灌洗中的白细胞计数显示，与对照组动物的肺相比，口服MAG-EPA处理可减少OVA致敏豚鼠在肺中的炎症细胞募集。结果还显示，在用MAG-EPA处理的OVA致敏动物中，粘蛋白生成和MUC5AC表达水平降低。 MAG-EPA处理后，促炎性标志物（如IL-5，嗜酸性粒细胞趋化因子，IL-13和IL-4）的转录水平显着降低。此外，在OV-致敏动物中，口服MAG-EPA可以减少COX2过表达。结论与临床意义：我们证明MAG-EPA降低了OVA致敏动物的气道高反应性和肺部炎症，这一发现与IL-4，IL-5，IL-13，COX-2和MUC5AC表达水平的降低相一致。肺。目前的数据表明，MAG-EPA代表了解决过敏性哮喘炎症的新的潜在治疗策略。

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