Basic & Clinical Medicine ›› 2010, Vol. 30 ›› Issue (3): 246-251.

• 研究论文 • Previous Articles     Next Articles

Heme oxygenase-1 downregulates mucous hypersecretion induced by cigarette smoke in A549 cells

Rui-xia LEI, Xiang-dong ZHOU   

  1. Department of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University Department of Respiratory Medicine,the Second Affiliated Hospital,Chongqing Medical University
  • Received:2009-07-27 Revised:2009-10-10 Online:2010-03-05 Published:2011-05-04
  • Contact: Xiang-dong ZHOU

Abstract: Objective To investigate the effects of heme oxygenase-1(HO-1) on the signal transduction pathway of mucin(MUC) expression induced by cigarette smoke. Methods The cell model of mucous hypersecretion was made by human lung A549 cell stimulated by cigarette smoke extract(CSE), the cells were divided into 4 groups: a negative control group, a CSE treatment group, an hemin pre-treatment group and a ZnPPIX pre-treatment group. The expression of MUC5AC, epidermal growth factor receptor(EGFR), p-EGFR, HO-1 and dual oxidase 1(Duox1) were detected. The cell activity was assessed by methyl thiazolyl tetrazolium method. The changes of HO-1 mRNA, Duox1 mRNA, EGFR mRNA and MUC5AC mRNA were examined by the use of reverse transcriptase-polymerase chain reaction. The protein expression changes of EGFR, p-EGFR, Duox1 and HO-1 were measured by Western blot, while the protein expression changes of MUC5AC were detected by enzyme-linked immunosorbent assay. Results The expression levels of MUC5AC mRNA and its protein in the CSE group were 0.660+0.044 and 157+3 ?g/mg, both increased significantly (P<0.05) as compared to those in the control group[0.412+0.043, (105+8) ?g/mg]. And the mRNA and protein of EGFR, Duox1 and HO-1, the protein of p-EGFR increased significantly as compared to the control group. After the cells were pre-treated with hemin, the mRNA and protein of HO-1 increased significantly, while the mRNA and protein of Duox1, EGFR and MUC5AC, the protein of p-EGFR decreased significantly as compared to the CSE group. After the cells were pre-treated with ZnPPIX, the increase of HO-1 mRNA and protein were not significant as compared to the control group, while the mRNA and protein of Duox1, EGFR and MUC5AC, the protein of p-EGFR increased significantly. Conclusions HO-1 decreased the level of Duox1, blocked ligand-dependent EGF-R activation,decreased the expression levels of MUC5AC.

Key words: mucins, cigarette smoke, receptor, epidermal growth factor, heme oxygenase-1

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