Molecular mechanisms of alveolar epithelial healing process in acute lung injury

1)角质形成细胞生长因子(KGF)是促进肺泡II型细胞增殖和分化的重要因子。2)气管内滴注KGF可预防博莱霉素和盐酸所致的急性肺损伤。2.据报道，丙酮酸乙酯通过抑制核因子-kB发挥抗炎作用。我们证实，用肿瘤坏死因子α(TNFa)处理培养的肺泡上皮细胞可增加核因子-kB/DNA结合活性，而与丙酮酸乙酯孵育可强烈抑制这种结合活性。我们还证明了丙酮酸乙酯与RelA和p50相互作用，在多个点上抑制了它们的功能。3.嗜肺军团菌有鞭毛，引起肺纤维化。肺泡上皮细胞基因芯片分析表明，鞭毛蛋白可使肺泡上皮细胞纤维连接蛋白水平升高，E-钙粘蛋白水平降低，提示鞭毛蛋白与转化生长因子-β协同作用，诱导肺泡上皮细胞内皮细胞转化，导致肺纤维化。

1. We have demonstrated that 1) keratinocyte growth factor (KGF) is a potent factor for proliferation and differentiation of alveolar type II cells, 2) intratracheal instillation of KGF prevented acute lung injury by bleomycin and HCl. 2. Ethyl pyruvate reportedly has anti-inflammatory actions through inhibition of NF-kB. We confirmed that treatment of cultured alveolar epithelial cells with tumor necrosis factor a (TNFa) increased the NF-kB/DNA-binding activity, which was strongly inhibited with incubating with ethyl pyruvate. We also demonstrated that ethyl pyruvate interacts with RelA and p50 to inhibit their functions at multiple points. 3. Legionella pneumophila has flagella, causes pulmonary fibrosis. Microarray analysis in cultured alveolar epithelial cells indicated that flagellin increased fibronectin level and reduced E-cadherin level, which suggested that flagellin cooperates with TGF-b and induces EMT in alveolar epithelial cells, and causes fibrosis.