Gaseous nitrogen oxides stimulate cell cycle progression by retinoblastoma phosphorylation via activation of cyclins/Cdks [correction]

Abstract

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 retinoblastoma (Rb) phosphorylation via activation of cyclin-cell division protein kinase (cdk) complexes [correction]. Western blot and immunoprecipitation data showed that NOx gas increased the expressions of cyclinA/cdk2, cyclinD1/cdk4, and cyclinE/cdk2 complexes in the cells at 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 that induced lung fibroblast cell proliferation by stimulation of cell-cycle progression may contribute to lung fibrosis by NOx pollutants.