Ginsenoside metabolites Compound K suppress TNF-α-induced RANTES secretion in human bronchial epithelial cell line / 第二军医大学学报

ABSTRACT

Objective To explore the effects of ginsenoside metabolite Compound K (CK) on TNF-α-induced RANTES secretion in human bronchial epithelial cell line BEAS-2B and to elucidate its possible mechanism. Methods BEAS-2B cells were cultured and treated with CK in different dosages, and then the secretion of RANTES in BEAS-2B cells exposed to inflammatory stimuli was measured by ELISA kits. Expressions of RANTES mRNA and protein were detected by RT-PCR and Western blotting analysis, respectively. Reporter gene assay was employed to elucidate the interaction between CK and activator protein 1(AP-1), glucocorticoid receptor (GR). CK antagonist mifepristone was used to observe whether the inhibitory effect of CK against RANTES was mediated by GR. Results TNF-α-induced secretion of RANTES in BEAS-2B was markedly inhibited by CK (3-30 μmol/L). Treatment with CK also reduced RANTES mRNA and protein expression. Reporter gene assays indicated that CK was a GR agonist and could repress TNF-α-induced AP-1 transactivation. The inhibitory effects of CK on RANTES secretion were antagonized by mifepristone, suggesting a pivotal role of GR. Conclusion These results suggest that CK may inhibit TNF-α-induced RANTES secretion in human bronchial epithelial cells, which might be associated with GR pathway activation and AP-1 pathway inhibition.