title: Trichloroethanol up-regulates matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in HaCaT cells.
abstract: Occupational trichloroethylene (TCE) exposure could induce generalized skin hypersensitivity reactions complicated with severe liver dysfunctions. Active extracellular matrix degradation and remodeling are involved in the skin hypersensitivity reaction induced by chemical exposure. In the present study, we have compared the effects of in vitro exposure to trichloroethanol (TCOH) and trichloroacetic acid (TCA) of a keratinocyte cell line (HaCaT). The modulation of matrix metalloproteinases (MMPs) was selected as marker of sensitization. HaCaT cells were treated with different concentrations of TCOH or TCA up to 6days. The gelatinolyic activities of MMP-2 and MMP-9 were detected by gelatin-zymography. MMP-2, tissue inhibitor of metalloproteinase (TIMP)-2, MMP-9 and TIMP-1 mRNAs were analyzed by real-time PCR and MMP-9 and TIMP-1 proteins were tested by Western blotting. A dose-effect relationship between TCOH treatment and MMP-9 activity, mRNA and protein expression levels was found in HaCaT cells. TCOH also induced up-regulation of TIMP-1 mRNA and protein. We found no such effects in HaCaT cells treated with TCA. Moreover, previously published literatures on patch tests suggested that TCOH could induce moderately positive reactions at low concentrations in hypersensitivity patients caused by occupational TCE exposure. In summary, these observations indicated that TCOH might play an important role in TCE-induced skin hypersensitivity.
authors: National Institute for Occupational Health and Poison Control, Key Laboratory of Chemical Safety and Health, Chinese Center for Disease Control and Prevention, Beijing, China.
authors: Haijun
authors: H
authors: Yang
authors: Yufei
authors: Y
authors: Dai
authors: Haiyan
authors: H
authors: Dong
authors: Dan
authors: D
authors: Zang
authors: Qing
authors: Q
authors: Liu
authors: Huawei
authors: H
authors: Duan
authors: Yong
authors: Y
authors: Niu
authors: Ping
authors: P
authors: Bin
authors: Yuxin
authors: Y
authors: Zheng
mesh_terms: D000395:Air Pollutants, Occupational / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005023:Ethylene Chlorohydrin / Q000031:analogs & derivatives* / Q000633:toxicity; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis* / Q000235:genetics; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D014238:Trichloroacetic Acid / Q000633:toxicity; D014241:Trichloroethylene / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000395:Air Pollutants, Occupational; D012333:RNA, Messenger; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D014241:Trichloroethylene; D014238:Trichloroacetic Acid; D005023:Ethylene Chlorohydrin; C005849:2,2,2-trichloroethanol; D020780:Matrix Metalloproteinase 9