title: Chlorpyrifos induces NLRP3 inflammasome and pyroptosis/apoptosis via mitochondrial oxidative stress in human keratinocyte HaCaT cells.
abstract: Chlorpyrifos (CPF) has been widely used around the world as a pesticide for both agricultural and residential application. Although various studies have reported toxicity and health-related effects from CPF exposure, the molecular mechanism of CPF toxicity to skin has not been well-characterized. The present study determined the potential mechanism involved in skin toxicity of CPF using the HaCaT human skin keratinocyte cell line. After treating to HaCaT cells, CPF triggered reactive oxygen species (ROS) generation and mitochondrial oxidative stress. We focused on NLRP3 inflammasome, known to induce innate immune response. We used mitochondrial ROS (mROS) scavenger mitoTEMPO to demonstrate a role for mROS in NLRP3 inflammasome and programmed cell death induced by CPF. Our results showed that CPF provoked NLRP3 inflammasome and pyroptosis/apoptosis via an increase of mROS in HaCaT cells. This study proposes that CPF induces innate immune response and skin inflammation through activating the NLRP3 inflammasome in skin epithelial cells. CPF may lead to cutaneous disease conditions and antioxidants could be proposed for therapy against skin exposure to CPF.
authors.affiliation: Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul 08826 South Korea.
authors.forename: Yoonjeong
authors.initials: Y
authors.lastname: Jang
authors.affiliation: Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul 08826 South Korea.
authors.forename: Ah Young
authors.initials: AY
authors.lastname: Lee
authors.affiliation: Department of Bio Applied Toxicology, Hoseo Toxicology Research Center, Hoseo University, Asan 31499, South Korea.
authors.forename: Sang-Hee
authors.initials: SH
authors.lastname: Jeong
authors.affiliation: National Institute of Agricultural Science, Rural Development Administration, Jeonju 54875, South Korea.
authors.forename: Kyung-Hun
authors.initials: KH
authors.lastname: Park
authors.affiliation: National Institute of Agricultural Science, Rural Development Administration, Jeonju 54875, South Korea.
authors.forename: Min-Kyoung
authors.initials: MK
authors.lastname: Paik
authors.affiliation: National Institute of Agricultural Science, Rural Development Administration, Jeonju 54875, South Korea.
authors.forename: Nam-Joon
authors.initials: NJ
authors.lastname: Cho
authors.affiliation: Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul 08826 South Korea. Electronic address: purin77@snu.ac.kr.
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul 08826 South Korea; Graduate School of Convergence Science and Technology, Seoul National University, Suwon 16229, South Korea; Graduate Group of Tumor Biology, Seoul National University, Seoul 08826, South Korea; Advanced Institute of Convergence Technology, Seoul National University, Suwon 16229, South Korea; Institute of GreenBio Science Technology, Seoul National University, Pyeongchang 25354, South Korea. Electronic address: mchotox@snu.ac.kr.
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D061945:Caspase Inhibitors / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004390:Chlorpyrifos / Q000633:toxicity*; D003877:Dermatitis, Contact / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D058847:Inflammasomes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D018384:Oxidative Stress / Q000187:drug effects*; D010575:Pesticides / Q000633:toxicity*; D000069292:Pyroptosis / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D018570:Risk Assessment; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002352:Carrier Proteins; D061945:Caspase Inhibitors; D016166:Free Radical Scavengers; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D010575:Pesticides; D017382:Reactive Oxygen Species; D004390:Chlorpyrifos
keywords: Chlorpyrifos; Inflammasome; Mitochondrial oxidative stress; Pyroptosis; Skin inflammation