title: Benomyl-induced effects of ORMDL3 overexpression via oxidative stress in human bronchial epithelial cells.
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.
authors: College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea.
authors: Yoonjeong
authors: Y
authors: Jang
authors: College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea.
authors: Ah Young
authors: AY
authors: Lee
authors: College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea.
authors: Ji-Eun
authors: JE
authors: Kim
authors: Department of Bio Applied Toxicology, Hoseo Toxicology Research Center, Hoseo University, Asan 31499, Republic of Korea.
authors: Sang-Hee
authors: SH
authors: Jeong
authors: R&D Center, Biterials, Goyang 10326, Republic of Korea. Electronic address: lifeisgood@biterials.com.
authors: Jun Sung
authors: JS
authors: Kim
authors: College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea. Electronic address: mchotox@snu.ac.kr.
authors: Myung-Haing
authors: MH
authors: Cho
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000975:Antioxidants / Q000494:pharmacology; D001542:Benomyl / Q000494:pharmacology*; D015153:Blotting, Western; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D016207:Cytokines; D008565:Membrane Proteins; C464399:ORMDL3 protein, human; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D050257:Tubulin Modulators; D051722:ADAM Proteins; C450441:ADAM33 protein, human; D001542:Benomyl
keywords: Benomyl; Human bronchial epithelial cells; ORMDL3; Reactive oxygen species