title: Toward elucidation of dioxin-mediated chloracne and Ah receptor functions.
abstract: Target cells and molecular targets responsible for dioxin-mediated chloracne, the hallmark of dioxin toxicity, are reviewed. The dioxin TCDD accumulates in sebum, and thereby persistently activates the Ah receptor (AhR), expressed in bipotential stem/progenitor cells of the sebaceous gland. AhR operates in cooperation with other transcription factors including c-Myc, Blimp1 and ß-Catenin/TCF: c-Myc stimulates exit of stem cells from quiescence to proliferating sebocyte progenitors; Blimp1 is a major c-Myc repressor, and ß-Catenin/TCF represses sebaceous gland differentiation and stimulates differentiation to interfollicular epidermis. TCDD has been demonstrated to induce Blimp1 expression in the sebocyte stem/progenitor cell line SZ95, leading to sebocyte apoptosis and proliferation of interfollicular epidermis cells. These findings explain observations in TCDD-poisoned individuals, and identify target cells and molecular targets of dioxin-mediated chloracne. They clearly demonstrate that the AhR operates in a cell context-dependent manner, and provide hints to homeostatic functions of AhR in stem/progenitor cells.
authors.affiliation: Department of Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Wilhelmstrasse 56, D-72074 Tübingen, Germany. Electronic address: bock@uni-tuebingen.de.
authors.forename: Karl Walter
authors.initials: KW
authors.lastname: Bock
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D054506:Chloracne / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D004147:Dioxins / Q000493:pharmacokinetics / Q000633:toxicity*; D006801:Humans; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D012627:Sebaceous Glands / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012629:Sebum / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D004147:Dioxins; D018336:Receptors, Aryl Hydrocarbon
keywords: 2,3,7,8-Tetrachlorodibenzo-p-dioxin=TCDD (PubChem CID 15625); 6-Formylindolo[3,2-b]carbazole=FICZ (PubChem CID 1863); Ah receptor; Blimp1; Chloracne; Sebocyte stem/progenitor cells; TCDD