Abstract：
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.
摘要：
杯状细胞增生和粘液产生增加是气道疾病的特征，包括哮喘,和过量的气道粘液经常恶化这些条件。甚至类固醇在严重哮喘的粘液产生中也不是统一有效的，需要新的治疗选择。Seihaito是一种日本传统医学，临床上用作镇咳和祛痰药。在本研究中,我们研究了Seihaito对杯状细胞分化和粘液产生的影响。在体外研究中，利用气-液界面培养豚鼠气管上皮细胞,Seihaito抑制IL-13诱导的杯状细胞和MUC5AC的增殖，粘液产生的主要组成部分。Seihaito抑制杯状细胞特异性基因表达，不改变睫状细胞特异性基因，表明它抑制杯状细胞分化。此外,Seihaito抑制了用SPDEF转染的细胞中MUC5AC的表达，由IL-13激活的转录因子。此外，Seihaito在IL-13处理的小鼠肺中减弱了体内杯状细胞增殖和MUC5ACmRNA表达。总的来说，这些发现表明Seihaito对杯状细胞分化和粘液产生具有抑制作用，这至少部分是由于SPDEF的抑制。
