title: Abnormal expression of MAPK, EGFR, CK17 and TGk in the skin lesions of chloracne patients exposed to dioxins.
abstract: OBJECTIVE
  Chloracne is one of the most sensitive and specific hallmark of dioxin intoxication. Although its clinical features are clearly described, poor understanding of the molecular pathways of dioxin-induced chloracne hampers a rational approach to therapy. The aim of the present study was to investigate the role of EGFR, MAPK, CK17, and TGk in the pathogenesis of chloracne related to dioxin exposures.
  
  
  METHODS
  Epidermal tissues of twelve chloracne patients exposed to dioxins were compared with tissues from 12 healthy controls. These skin tissues were obtained by punch biopsies. p-EGFR and p-MAPK were examined by immunofluorescence. The mRNA and protein levels of CK17 and TGk were examined by fluorescence in situ hybridization and immunohistochemistry, respectively.
  
  
  RESULTS
  p-EGFR and p-MAPK were found in all chloracne tissues, whereas no expression was found in the controls. CK17 mRNA and protein were also found in all chloracne lesions, but none in controls (P=0.000). TGk mRNA and protein were detected in both groups, but the distribution was distinct. The positive signals in the controls were mainly in the stratum granulosum, while in the chloracne tissues, the positive signals were found more significantly in the stratum granulosum and stratum spinosum.
  
  
  CONCLUSIONS
  The results demonstrate that in the human skin the activation of mitogen-activated protein kinase pathway and up-regulation of CK17 and TGK may play roles in the pathogenesis of chloracne related to dioxin exposures.
authors.affiliation: Department of Occupational Health, School of Public Health, Tianjin Medical University, 22# Qixiangtai Road, Tianjin 300070, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Chun-mei
authors.initials: CM
authors.lastname: Zhang
authors.forename: Pieter-Jan
authors.initials: PJ
authors.lastname: Coenraads
authors.forename: Zhi-ying
authors.initials: ZY
authors.lastname: Ji
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Dong
authors.forename: Xiao-ming
authors.initials: XM
authors.lastname: Ma
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.forename: Nai-jun
authors.initials: NJ
authors.lastname: Tang
mesh_terms: D000428:Alcohol Drinking / Q000378:metabolism; D054506:Chloracne / Q000378:metabolism*; D004147:Dioxins / Q000633:toxicity*; D004817:Epidermis / Q000378:metabolism; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053537:Keratin-17 / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis* / Q000235:genetics; D016273:Occupational Exposure; D012867:Skin / Q000201:enzymology / Q000378:metabolism*; D012907:Smoking / Q000378:metabolism; D011503:Transglutaminases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D004147:Dioxins; D053537:Keratin-17; D011503:Transglutaminases; C105804:transglutaminase 1; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases