Induction of MUC5AC mucin expression by histamine through the activation of its core promoter region

Abstract

Conclusion: This study provides evidence that histamine induced MUC5AC mRNA expression through the activation of the core region of its promoter. It may also help in approaching new therapeutic strategies in airway mucins hypersecretory diseases. Objective: Mucin hypersecretion characterizes several respiratory diseases. Production of MUC5AC, a major gel forming mucin secreted by airway epithelia, can be induced by various inflammatory mediators. Histamine is associated with MUC5AC up-regulation during the early phase of allergic respiratory diseases. The goal of the present study was to identify whether histamine may induce MUC5AC gene expression both at mRNA and protein levels and to elucidate its mechanism. Methods: Guinea pigs were sensitized and challenged with dermatophagoides farinae (Der f) extract. Human lung mucoepidermoid carcinoma cell line (NCI-H292) was used. The regulatory mechanism of MUC5AC by histamine and H1R was investigated using RT-PCR, immunofluorescence, and MUC5AC promoter-driven luciferase reporter assay. Results: The MUC5AC expression levels were increased by histamine treatment in either nasal tissues of Der f challenged guinea pigs or NCI-H292 cells, whereas the MUC5AC protein over-production induced by histamine administration was significantly inhibited by H1R antagonist chlorpheniramine. It was found that histamine enhanced the activation of the proximal core region of the MUC5AC promoter, which was significantly blocked by chlorpheniramine, as indicated by luciferase reporter assays.