Berberine suppresses interleukin-1β-induced MUC5AC gene expression in human airway epithelial cells

Abstract

Berberine is a bitter-tasting, yellow plant alkaloid with a long history ofmedicinal use in Chinese and Ayurvedic medicine. There is some evidence tosupport its use in the treatment of heart failure, malaria, diabetes, glaucoma,hypercholesterolemia, diarrhea, trachoma, and leishmaniasis. Traditionally, it hasbeen used as anti-fungal, anti-inflammatory, anti-viral agents, and also inrespiratory disorders. However, there is no evidence that berberine can suppressmucin secretion in human airway. Therefore, the aim of this study was toinvestigate whether berberine suppresses IL-1β-induced MUC5AC gene expressionin human airway epithelial cells and, if so, to examined which mitogen-activatedprotein kinases (MAPKs) were related to MUC5AC gene suppression. MUC5ACmRNA and protein were measured using reverse transcription-polymerase chainreaction (RT-PCR), real-time PCR, and western blot analysis in culturedNCI-H292 human airway epithelial cells. Extracellular signal-regulated kinase(ERK) and p38 MAPK protein levels were analyzed by Western blot. When thecells were pretreated with 25 μM of berberine, expression of IL-1β-inducedMUC5AC mRNA and protein was significantly suppressed compared to the controlgroup. MAPKs proteins were determined by Western blot analysis afterpretreatment with 25 μM berberine. Berberine suppressed phosphorylation ofextracellular signal regulated kinase (ERK) and p38 MAPK, but there was nochange in the expression of α-tubuline. Suppression of IL-1β-induced MUC5ACmRNA was also observed in cells pretreated with ERK- or p38 MAPK-specificinhibitors, suggesting that berberine suppression of IL-1β- induced MUC5ACmRNA operated via the ERK- and p38 MAPK-dependent pathways. Berberinesuppresses IL-1β-induced MUC5AC gene expression in human airway epithelialcells via the ERK- and p38 MAPK-dependent pathways. Therefore, berberine maybe considered a possible anti-hypersecretory agent.