Benzisothiazolinone upregulates the MUC5AC expression via ERK1/2, p38, and NF-κB pathways in airway epithelial cells

• Published in: Toxicology research (Cambridge) 2019-09, Vol.8 (5), p.704-710
• Main Authors: Kwak, Soyoung, Choi, Yoon Seok, Bae, Chang Hoon, Song, Si-Youn, Kim, Hyung Geun, Kim, Yong-Dae
• Format: Article
• Language: English
• Subjects: Asthma; Chemistry; Epithelial cells; Extracellular signal-regulated kinase; Human performance; In vivo methods and tests; Inflammatory diseases; Kinases; Lymphocytes B; Mucin; Mucus; NF-κB protein; Phosphorylation; Respiratory tract; Respiratory tract diseases
• ISSN: 2045-4538; 2045-452X; 2045-4538
• DOI: 10.1039/c9tx00135b

Mucus plays an important role in protecting the respiratory tract from irritants. However, mucus hypersecretion is a major indicator of airway diseases. 1,2-Benzisothiazolin-3-one (BIT), as a microbicide, induces asthmatic inflammation. Therefore, we focused on the effects of BIT-related mucin secretion in airway epithelial cells. Our in vivo study showed increased mucus and MUC5AC expressions in the bronchioles of mice that inhaled BIT. For investigating the signaling pathways, we performed experiments in human airway epithelial cells. BIT induced the MUC5AC expression and significantly increased the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). The specific inhibitors of ERK1/2, p38, and NF-κB blocked the BIT-induced MUC5AC expression. Therefore, these results suggest that BIT induces the MUC5AC expression via the ERK1/2, p38, and NF-κB pathways in human airway epithelial cells, which may be involved in mucus hypersecretion associated with airway inflammatory diseases.