title: Trifloxystrobin induces tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in HaCaT, human keratinocyte cells.
abstract: As the outermost layer of the body, the skin plays an important role in exposure to pesticides, which could have negative impacts on human health. Trifloxystrobin is a widely used fungicide of the strobilurin class, however, there is little information regarding the skin contact-associated toxic mechanism. Therefore, the present study was performed in order to identify the skin toxicity mechanism of trifloxystrobin using HaCaT (keratinocyte of human skin) cells. Following 24 or 48 h treatment, cell viability, and subsequent Annexin V-FITC/propidium iodide assay, TUNEL assay and Western blotting were performed to investigate the cell death mechanism of trifloxystrobin. Exposure to trifloxystrobin resulted in diminished viability of HaCaT cells in both a time- and concentration-dependent manner. The cell death was derived through apoptotic pathways in the HaCaT cells. Furthermore, we explored the effect of trifloxystrobin on TRAIL-mediated extrinsic apoptosis using siRNA transfection. Knockdown of death receptor 5 suppressed trifloxystrobin-provoked apoptosis. These results indicate that trifloxystrobin induces TRAIL-mediated apoptosis and has an inhibitory effect in keratinocytes that can interfere with the barrier function and integrity of the skin. This could be proposed as a mechanism of skin toxicity by trifloxystrobin and considered in the management of pesticide exposure.
authors.affiliation: a 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 , Korea.
authors.forename: Yoonjeong
authors.initials: Y
authors.lastname: Jang
authors.affiliation: a 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 , Korea.
authors.forename: Ah Young
authors.initials: AY
authors.lastname: Lee
authors.affiliation: a 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 , Korea.
authors.forename: Seung-Hee
authors.initials: SH
authors.lastname: Chang
authors.affiliation: b Department of BioApplied Toxicology , Hoseo Toxicology Research Center, Hoseo University , Asan , Korea.
authors.forename: Sang-Hee
authors.initials: SH
authors.lastname: Jeong
authors.affiliation: c Rural Development Administration, National Institute of Agricultural Science , Jeonju , Korea.
authors.forename: Kyung-Hun
authors.initials: KH
authors.lastname: Park
authors.affiliation: c Rural Development Administration, National Institute of Agricultural Science , Jeonju , Korea.
authors.forename: Min-Kyoung
authors.initials: MK
authors.lastname: Paik
authors.affiliation: c Rural Development Administration, National Institute of Agricultural Science , Jeonju , Korea.
authors.forename: Nam-Joon
authors.initials: NJ
authors.lastname: Cho
authors.affiliation: a 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 , Korea.
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: a 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 , Korea.|d Graduate School of Convergence Science and Technology, Seoul National University , Suwon , Korea.|e Graduate Group of Tumor Biology, Seoul National University , Seoul , Korea.|f Advanced Institute of Convergence Technology, Seoul National University , Suwon , Korea , and.|g Institute of GreenBio Science Technology, Seoul National University , Pyeongchang , Korea.
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
mesh_terms: D000085:Acetates / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005659:Fungicides, Industrial / Q000633:toxicity*; D006801:Humans; D007097:Imines / Q000633:toxicity*; D020287:In Situ Nick-End Labeling; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008689:Methacrylates / Q000633:toxicity; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D000073739:Strobilurins; D013997:Time Factors
chemical_list: D000085:Acetates; D005659:Fungicides, Industrial; D007097:Imines; D008689:Methacrylates; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D000073739:Strobilurins; C467051:trifloxystrobin
keywords: TRAIL-mediated apoptosis; Trifloxystrobin; keratinocyte