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本文探讨TLR2是否介导博莱霉素(BLM)诱导的急性肺损伤、炎症与纤维化的发生。流式细胞术用于检测树突状细胞(DCs)成熟;ELISA方法检测细胞因子分泌;Western blotting检测蛋白表达与活化。小鼠气管内注入BLM制备急性肺损伤模型。结果表明,模型小鼠肺局部高表达TLR2(P<0.001)及其相关信号分子。阻断TLR2显著抑制BLM诱导的DCs成熟及细胞因子IL-6(P<0.001),IL-17(P<0.05)与IL-23(P<0.05)的分泌。阻断TLR2不仅抑制支气管肺泡灌洗液中炎性细胞的增加,而且还增强TH1(P<0.05),抑制TH2(P<0.001)、Treg(P<0.01)与TH17(P<0.01)反应。重要的是,阻断TLR2可显著减轻肺损伤、炎症与纤维化,提高动物的生存率(从50%到92%,P<0.01)。结果提示,TLR2可作为治疗急性肺损伤与肺纤维化的潜在药物靶点。
This article investigates whether TLR2 mediates bleomycin (BLM) -induced acute lung injury, inflammation and fibrosis. Flow cytometry was used to detect the maturation of dendritic cells (DCs); ELISA was used to detect cytokine secretion; Western blotting was used to detect protein expression and activation. Acute lung injury model was induced by intratracheal instillation of BLM in mice. The results showed that TLR2 (P <0.001) and its related signaling molecules were highly expressed in lung of model mice. Blockade of TLR2 significantly inhibited BLM-induced maturation of DCs and secretion of cytokines IL-6 (P <0.001), IL-17 (P <0.05) and IL-23 (P <0.05). Blocking TLR2 not only inhibited the increase of inflammatory cells in bronchoalveolar lavage fluid, but also enhanced TH1 (P <0.05), inhibited TH2 (P <0.001), Treg (P <0.01) and TH17 (P <0.01). Importantly, blockade of TLR2 significantly reduced lung injury, inflammation and fibrosis, and increased animal survival (from 50% to 92%, P <0.01). The results suggest that TLR2 can be used as a potential drug target for the treatment of acute lung injury and pulmonary fibrosis.