MS19通过抑制IRF5表达调控巨噬细胞极化减轻CTD-ILD肺部炎症的作用研究

Role of MS19 in alleviating lung inflammation in CTD-ILD by regulating macrophage polarization through inhibiting the expression of IRF5

目的 探讨MS19通过靶向干扰素调节因子5(IRF5)对结缔组织疾病相关肺间质病变(CTD-ILD)小鼠模型肺部炎症的治疗作用及其相关机制。方法 动物实验:构建CTD-ILD小鼠模型,予以MS19干预,研究MS19对CTD-ILD小鼠肺部炎症的影响。细胞实验:对RAW264.7细胞进行OE-IRF5转染,然后予以MS19干预,研究MS19对IRF5调控的巨噬细胞M1型极化及炎症反应的影响。结果 动物实验:CTD-ILD小鼠出现明显的肺部炎症,小鼠支气管肺泡灌洗液(BALF)中IRF5的表达增高、巨噬细胞M1型极化增加及促炎因子(TNF-α、IL-6和IL-1β)的表达升高;而MS19干预后,CTD-ILD小鼠的肺部炎症减轻,BALF中IRF5表达降低、巨噬细胞M1型极化减少及促炎因子表达下降。细胞实验:脂多糖诱导巨噬细胞M1型极化、促炎因子表达增加;转染OE-IRF5后,巨噬细胞M1型极化增加、促炎因子表达增加;MS19干预后,巨噬细胞M1型极化减少、促炎因子表达减少。结论 MS19通过靶向抑制IRF5调控巨噬细胞极化及炎症反应,从而改善CTD-ILD的肺部炎症,为防治CTD-ILD提供潜在靶点和候选药物。

Objective To determine the therapeutic effect of MS19 on pulmonary inflammation in mice with connective tissue disease related interstitial lung disease(CTD-ILD)by targeting IRF5 and related mechanism.Methods Animal experiments:CTD-ILD mouse models were constructed and treated with MS19 to determine the effect of MS19 on pulmonary inflammation in CTD-ILD mice.Cell experiments:RAW264.7 cells were transfected with OE-IRF5,and then treated with MS19 to study the effect of MS19 on IRF5-mediated M1 polarization and inflammatory responses of the macrophages.Results Animal experiments:CTD-ILD mice showed significant pulmonary inflammation,with elevated expression of IRF5,M1 polarization of macrophages,and expression of pro-inflammatory cytokines(TNF-α,IL-6,and IL-1β)in bronchoalveolar lavage fluid(BALF).While the CTD-ILD mice treated with MS19,their pulmonary inflammation was alleviated,and expression of IRF5,M1 polarization of macrophages and expression of pro-inflammatory cytokines were all decreased in BALF.Cell experiments:LPS induced an increase in M1 polarization and expression of pro-inflammatory cytokines in the macrophages.After transfection of OE-IRF5,M1 polarization of macrophages and expression of pro-inflammatory cytokines increased.After the MS19 treatment,M1 polarization of macrophages and expression of pro-inflammatory cytokines decreased.Conclusion MS19 improves pulmonary inflammation in CTD-ILD by targeting and inhibiting IRF5,thereby providing potential targets and candidate drugs for the prevention and treatment of CTD-ILD.