Rapid, Non-genomic Reduction of Intracelluar[Ca2+] and Mucin Secretion by Steroid Hormones in Human Nasal Epithelial Cells

Kim, Tae Hwan; Kim, Dae Ran; Cha, Seung Kyu; Moon, Jeong Hun; Kim, Sung Il; Park, Dong Joon

Abstract

BACKGROUND AND OBJECTIVES
Airway mucus hypersecretion is one of the major clinical manifestation of patients suffering from various upper or lower respiratory tract diseases. But unfortunately, no drugs are yet available for controlling the airway mucus hypersecretion. Although pharmacological approaches for controlling airway mucus production is currently limited, among the few useful drugs, steroid hormones seem to be the most effective. The effect of steroid hormones is classically described as that of a genomic mechanism involving nucleus transcription. but there is a growing evidence for rapid, non-genomic effect of steroid hormones working through various second messenger systems and ion transporters. MATERIALS AND METHOD: In order to investigate a possible rapid, non-genomic effect of dexamethasone and aldosterone in cultured normal human nasal epithelial (NHNE) cell, the effect of dexamethasone and aldosterone was tested for intracellular calcium response (delta[Ca2+]i) and mucin secretion to external ATP, a known secretagogue in airway epithelial cells, with fluorescence imaging system and ELISA, respectively. Also, we demonstrated the effect of dexamethasone on the mRNA expression of MUC5AC mucin gene for evidence of the existence of non-genomic mechanism of steroid hormones in NHNE cells. RESULTS: Pretreatment with dexamethasone or aldosterone with various concentrations and duration caused a reduction in the delta[Ca2+]i and mucin secretion to ATP. In RT-PCR, Ten minutes dexamethasone pretreatment did not attenuate the mRNA expression of MUC5AC mucin gene, but 24 hours of dexamethasone pretreatment did so. These data indicate that a few minutes of steroid hormone pretreatment can decrease the delta[Ca2+]i and mucin secretion via a non-genomic mechanism. CONCLUSION: In this study, we confirmed the rapid, non-genomic effect of steroid hormones in NHNE cells and suggest this study as a research model for developing antisecretory drugs that have rapid effect.