Bisacodyl Suppresses TGF-α-Induced MUC5AC Production in NCI-H292 Cells.

MUC5AC overproduction is commonly observed in chronic inflammatory lung diseases and worsens these conditions. Therefore, drugs that inhibit MUC5AC production are urgently needed. To identify novel drugs directly inhibiting MUC5AC production, 640 already approved drugs were screened. We found that the laxative bisacodyl suppressed transforming growth factor (TGF)-α-induced MUC5AC production in a concentration-dependent manner. Additionally, bisacodyl also suppressed TGF-α-induced MUC5AC mRNA expression in the same concentration range. These results suggested that bisacodyl could be a new drug for treating mucin overproduction.

Ibudilast Suppresses MUC5AC Mucus Production through Inhibition of ERK1/2 Phosphorylation.

Mucus hypersecretion is a hallmark of respiratory diseases, and excess airway mucus can worsen these conditions. Therefore, it is important to control the production of airway mucus in the treatment of respiratory diseases. The phosphodiesterase inhibitor ibudilast has been reported to be effective in treating sputum and postnasal drip in patients with chronic airway inflammation. On the basis of the hypothesis that ibudilast could inhibit mucus production in the airway, in the present study, we examined the effects of ibudilast on the production of MUC5AC, a major protein component of mucus. In in vitro studies using NCI-H292 cells, ibudilast suppressed MUC5AC production induced by various stimuli. In addition, ibudilast inhibited extracellular signal-regulated kinase (ERK)1/2 phosphorylation and MUC5AC gene transcription. Furthermore, it attenuated MUC5AC production and Muc5ac mRNA expression in lipopolysaccharide-treated mice in vivo. Collectively, these findings demonstrate that ibudilast has an inhibitory effect on mucus production, which could at least partly be attributed to the inhibition of ERK1/2 phosphorylation and the repression of MUC5AC gene transcription.