RESUMO
Goblet cell hyperplasia and increased mucus production are features of airway diseases, including asthma, and excess airway mucus often worsens these conditions. Even steroids are not uniformly effective in mucus production in severe asthma, and new therapeutic options are needed. Seihaito is a Japanese traditional medicine that is used clinically as an antitussive and expectorant. In the present study, we examined the effect of Seihaito on goblet cell differentiation and mucus production. In in vitro studies, using air-liquid interface culture of guinea-pig tracheal epithelial cells, Seihaito inhibited IL-13-induced proliferation of goblet cells and MUC5AC, a major component of mucus production. Seihaito suppressed goblet cell-specific gene expression, without changing ciliary cell-specific genes, suggesting that it inhibits goblet cell differentiation. In addition, Seihaito suppressed MUC5AC expression in cells transfected with SPDEF, a transcription factor activated by IL-13. Furthermore, Seihaito attenuated in vivo goblet cell proliferation and MUC5AC mRNA expression in IL-13-treated mouse lungs. Collectively, these findings demonstrated that Seihaito has an inhibitory effect on goblet cell differentiation and mucus production, which is at least partly due to the inhibition of SPDEF.
Assuntos
Diferenciação Celular , Proliferação de Células , Células Caliciformes , Interleucina-13 , Medicina Kampo , Metaplasia , Mucina-5AC , Muco , Animais , Células Caliciformes/efeitos dos fármacos , Células Caliciformes/patologia , Células Caliciformes/metabolismo , Interleucina-13/metabolismo , Mucina-5AC/genética , Mucina-5AC/metabolismo , Muco/metabolismo , Diferenciação Celular/efeitos dos fármacos , Cobaias , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Células Cultivadas , Proteínas Proto-Oncogênicas c-ets/genética , Proteínas Proto-Oncogênicas c-ets/metabolismo , Masculino , Expressão Gênica/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Camundongos , Traqueia/citologia , Traqueia/efeitos dos fármacos , Traqueia/patologia , Traqueia/metabolismoRESUMO
Airway ciliary cells are components of the mucociliary transport system and play an important role in sweeping out small particles, such as bacteria and viruses, towards the oropharynx by the action of beating cilia. Several lines of evidence have shown that the ciliary beat is under the regulation of the purinergic system; however, the subtype of receptor and the intracellular signaling pathways involved in the activation of ciliary movement remain to be elucidated. In addition, although the activity of ciliary movement comprises two parameters, the ciliary beat frequency (CBF) and ciliary bend angle (CBA), few reports have analyzed CBA. In this study, we examined the effects of ATP and other purinergic ligands on both CBF and CBA and demonstrated that the purinergic signaling requirements for CBF and CBA are different, with CBF mediated by P2Y1 receptor activation and CBA mediated by the P2X4 receptor.