OVEREXPRESSION OF MUCIN GENES INDUCED BY INTERLEUKIN1-1β, TUMOR NECROSIS FACTOR-α, LIPOPOLYSACCHARIDE, AND NEUTROPHIL ELASTASE IS INHIBITED BY A RETINOIC ACID RECEPTOR α ANTAGONIST

Abstract

Proinflammatory cytokines, lipopolysaccharide (LPS), and neutrophil elastase (NE) have been implicated in the induction of hypersecretion of respiratory mucus. In this study, we demonstrated that interleukin-1 β (IL-1 β) increased MUC2 and MUC5AC mRNA levels 2- to 3-fold in a time- and dose-dependent manner in NCI-H292 cells. In contrast, MUC5B mRNA was not significantly changed. A transcription inhibitor blocked the stimulation of MUC2 and MUC5AC gene expression by IL-1 β. A translation inhibitor did not interfere with the induction of MUC2 mRNA expression, whereas stimulation of MUC5AC mRNA was blocked, suggesting de novo protein synthesis is required for the stimulation of MUC5AC mRNA. We previously reported that induction of MUC2, MUC5AC, and MUC5B gene expressions by retinoic acid is mediated by the retinoic acid receptor (RAR α) , and inhibited by the specific RAR α antagonist Ro 41-5253. Here, we demonstrate that the RAR α antagonist can effectively inhibit IL-1 β -induced MUC2 and MUC5AC gene expression and reduce intracellular MUC5AC protein. Further investigation showed that the RAR α antagonist also inhibited the stimulation of MUC2 and MUC5AC mRNA expression by tumor necrosis factor- α, LPS, and NE.

• Bronchial Epithelium
• Mucin
• Mucous Hypersecretion
• Cytokine
• Interleukin-1BETA
• Retinoic Acid
• Retinoic Acid Receptor Antagonist