title: 2,3,7,8-Tetrachlorodibenzo-p-dioxin alters sebaceous gland cell differentiation in vitro.
abstract: Chloracne is a characteristic marker of intoxication by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or related compounds. Decreased lipogenesis is a prominent clinical sign in this disease. However, the activity of dioxins on human sebaceous glands is still unclear. In this study, the effects of TCDD on sebaceous gland differentiation were studied both in human skin samples maintained ex vivo and in cultured SZ95 sebocytes. Aryl hydrocarbon receptor (AhR) protein expression, the receptor for dioxin, was detected in SZ95 sebocytes. Its expression was markedly inhibited by TCDD. Furthermore, we detected a reduced release of neutral lipids (10(-10) -10(-8) M; P<0.001) and decreased expression of epithelial membrane antigen and keratin 7, all of which are specific markers of sebaceous differentiation. Markedly, increased expression of the keratinocyte differentiation marker keratin 10 and of peroxisome proliferators-activated receptor-δ was assessed in SZ95 sebocytes treated with TCDD. To corroborate these in vitro data, an ex vivo sebaceous gland-rich skin culture model was investigated. Obvious shrinkage of sebaceous glands with sebaceous duct hyperplasia and increased expression of keratin 10 in the atrophic sebaceous glands were observed on the 5th day of TCDD treatment. In conclusion, TCDD affects the differentiation of sebaceous gland cells probably by switching human sebaceous into keratinocyte-like differentiation. In addition and together with the results of a parallel study (J Dermatol Sci 58, 2010, 211), we provide evidence that TCDD effects on human sebocytes are mediated through the AhR signalling pathway.
authors.affiliation: Laboratory of Biogerontology, Dermato-Pharmacology and Dermato-Endocrinology, Institute of Clinical Pharmacology and Toxicology, Charité Universitaetsmedizin Berlin, Berlin, Germany.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ju
authors.forename: Sabine
authors.initials: S
authors.lastname: Fimmel
authors.forename: Norbert
authors.initials: N
authors.lastname: Hinz
authors.forename: Ralf
authors.initials: R
authors.lastname: Stahlmann
authors.forename: Longqing
authors.initials: L
authors.lastname: Xia
authors.forename: Christos C
authors.initials: CC
authors.lastname: Zouboulis
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D006801:Humans; D053550:Keratin-10 / Q000378:metabolism; D053552:Keratin-7 / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D018396:Mucin-1 / Q000378:metabolism; D047494:PPAR delta / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects / Q000378:metabolism*; D012627:Sebaceous Glands / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D053552:Keratin-7; D018396:Mucin-1; D047494:PPAR delta; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D053550:Keratin-10