氣體性氫氧化物(NOx)是室內外空氣中重要的汙染物質之一。許多研究指出，NOx氣體經由其氧化特性及其自由基來造成肺組織的傷害。在我們先前的研究已證實NOx氣體可誘導人類肺纖維細胞MRC-5的增生。在本研究結果發現，NOx氣體誘導人類肺纖維細胞MRC-5的增生是經由活化Cyclin-cdk complexes進而磷酸化Rb蛋白。本研究利用西方墨點法與免疫沉澱法證實：NOx氣體處理人類肺纖維細胞MRC-5後9小時可誘使細胞中CyclinA/cdk2、CyclinD1/cdk4、CyclinE/cdk2蛋白增加表現，Rb蛋白磷酸化增加，並且使cdk抑制蛋白p27、p16表現下降。這些結果顯示NOx氣體誘導人類肺纖維細胞MRC-5的增生是經由活化細胞週期蛋白Cyclin-cdk complexes，進而磷酸化Rb蛋白，並且抑制cdk抑制蛋白。總而言之，NOx氣體經由刺激細胞週期進行而誘導人類肺纖維細胞的增生可能與空氣汙染物質刺激肺部纖維化有關。 Nitrogen oxides (NOx) are important indoor and outdoor air pollutants. Many studies have indicated that NOx gas causes lung tissue damage by its oxidation properties and its free-radicals. In a previous study we demonstrated that NOx gas induced proliferation of human lung fibroblast MRC-5 cells. In this study we show that NOx gas stimulates MRC-5 cell proliferation by Rb phosphorylation via activation of cyclin-cdk complexes. Western blot and immunoprecipitation data showed that NOx gas increased the expressions of cyclinA/cdk2, cyclinD1/cdk4 and cyclinE/cdk2 complexes in the cells 9 h after treatment. The levels of phospho-Rb were also increased and cdk inhibitors (CKIs) p27 and p16 were apparently decreased. These data suggested that NOx gas stimulates cell cycle progression by Rb phosphorylation via activation of cyclin-cdk complexes and inhibition of CKIs. In conclusion, the NOx gas induced lung fibroblast cell proliferation by stimulation of cell cycle progression may contribute to lung fibrosis by NOx pollutants.
