Benomyl-induced effects of ORMDL3 overexpression via oxidative stress in human bronchial epithelial cells

• Published in: Food and chemical toxicology 2016-12, Vol.98 (Pt B), p.100-106
• Main Authors: Jang, Yoonjeong, Lee, Ah Young, Kim, Ji-Eun, Jeong, Sang-Hee, Kim, Jun Sung, Cho, Myung-Haing
• Format: Article
• Language: English
• Subjects: ADAM Proteins - genetics; ADAM Proteins - metabolism; Antioxidants - pharmacology; Benomyl; Benomyl - pharmacology; Blotting, Western; Bronchi - cytology; Bronchi - drug effects; Bronchi - metabolism; Cell Survival - drug effects; Cells, Cultured; Cytokines - genetics; Cytokines - metabolism; Epithelial Cells - cytology; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Gene Expression Regulation - drug effects; Human bronchial epithelial cells; Humans; Membrane Proteins - genetics; Membrane Proteins - metabolism; ORMDL3; Oxidative Stress - drug effects; Reactive oxygen species; Reactive Oxygen Species - metabolism; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Tubulin Modulators - pharmacology
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2016.10.024

The respiratory system is a major site of exposure route during pesticide use. Although pesticide exposure is associated with chronic respiratory diseases including asthma, the underlying pathophysiological mechanism remains to be elucidated. In this study, we investigated the in vitro effects of benomyl-induced ORMDL3 overexpression on the toxicological mechanism using the human bronchial epithelial cell line 16HBE14o-. Benomyl increased reactive oxygen species and Ca2+ levels, and asthma-related ADAM33 and ORMDL3 expression in 16HBE14o− cells. Considering the change in Ca2+ level and protein expression, we focused on ORMDL3 to elucidate the mechanism of benomyl-induced asthma. Antioxidant treatment showed that benomyl-induced ORMDL3 and endoplasmic reticulum stress could be triggered by oxidative stress. Furthermore, ORMDL3 knockdown alleviated the effects of benomyl on intracellular Ca2+, and the expression of metalloproteinases, and proinflammatory cytokines involved in the pathogenesis of asthma. In conclusion, our results suggest that benomyl-induced ORMDL3 overexpression via oxidative stress might be a mechanism involved in asthma. Moreover, antioxidants and alleviating mechanisms that reduce ORMDL3 levels could serve as promising therapeutic targets for pesticide-induced asthma. •Benomyl generates ROS in human bronchial epithelial cells 16HBE14o−.•Benomyl upregulates asthma-related proteins, ADAM33 and ORMDL3.•Antioxidants alleviate the effects of benomyl exposure in 16HBE14o− cells.•Metalloproteinases and cytokines involved in asthma pathogenesis could be proposed as downstream pathways of ORMDL3 overexpression by benomyl.