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

Soyoung Kwak; Yoon Seok Choi; Hyung Gyun Na; Chang Hoon Bae; Si-Youn Song; Hyung Geun Kim; Yong-Dae Kim

doi:10.1039/c9tx00135b

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

Toxicol Res (Camb). 2019 Jul 16;8(5):704-710. doi: 10.1039/c9tx00135b. eCollection 2019 Sep 1.

Authors

Soyoung Kwak^{1

2}, Yoon Seok Choi², Hyung Gyun Na², Chang Hoon Bae², Si-Youn Song², Hyung Geun Kim², Yong-Dae Kim^{2

3}

Affiliations

¹ Department of Medical Science , College of Medicine , Graduate School of Yeungnam University , Daegu , Republic of Korea.
² Department of Otorhinolaryngology-Head and Neck Surgery , College of Medicine , Yeungnam University , Daegu , Republic of Korea . Email: ydkim@med.yu.ac.kr ; ; Tel: +82-53-620-3781.
³ Regional Center for Respiratory Diseases , Yeungnam University Medical Center , Daegu , Republic of Korea.

Abstract

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.