Objectives:The aim of this study was to investigate whether berberine suppresses interleukin (IL)-1β-induced MUC5AC gene expression in human airway epithelial cells and, if so, to determine which mitogen-activated protein kinases (MAPKs) are related to MUC5AC gene suppression. Materials and Methods:MUC5AC mRNA and protein levels were measured using reverse transcription-polymerase chain reaction (PCR), real-time PCR, and western blot analysis in cultured NCI-H292 human airway epithelial cells. Results:IL-1β-induced expressions of MUC5AC mRNA and protein were significantly suppressed in cells pretreated with 25 μM of berberine. Levels of MAPK proteins were determined by western blot analysis after pretreatment with 25 μM berberine. Berberine suppressed phosphorylation of extracellular signal-regulated kinase (ERK) and p38 MAPK, but there was no change in the expression of JNK. Suppression of IL-1β-induced MUC5AC mRNA was also observed in cells pretreated with ERK- or p38 MAPK-specific inhibitors, suggesting that berberine suppresses IL-1β-induced expression of MUC5AC mRNA, which involves the ERK- and p38 MAPK-dependent pathways. Conclusion:Berberine suppresses IL-1β-induced MUC5AC gene expression in human airway epithelial cells via the ERK- and p38 MAPK-dependent pathways; therefore, berberine may be considered as a possible anti-hypersecretory agent for inflammatory airway diseases