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Food Chem Toxicol. 2016 Dec;98(Pt B):100-106. doi: 10.1016/j.fct.2016.10.024. Epub 2016 Oct 23.

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

Author information

1
College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea.
2
Department of Bio Applied Toxicology, Hoseo Toxicology Research Center, Hoseo University, Asan 31499, Republic of Korea.
3
R&D Center, Biterials, Goyang 10326, Republic of Korea. Electronic address: lifeisgood@biterials.com.
4
College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea. Electronic address: mchotox@snu.ac.kr.

Abstract

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.

KEYWORDS:

Benomyl; Human bronchial epithelial cells; ORMDL3; Reactive oxygen species

PMID:
27784618
DOI:
10.1016/j.fct.2016.10.024
[Indexed for MEDLINE]

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