title: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-mediated deregulation of myeloid and sebaceous gland stem/progenitor cell homeostasis.
abstract: Studies of TCDD toxicity stimulated identification of the responsible aryl hydrocarbon receptor (AHR), a multifunctional, ligand-activated transcription factor of the basic helix-loop-helix/Per-Arnt-Sim family. Accumulating evidence suggests a role of this receptor in homeostasis of stem/progenitor cells, in addition to its known role in xenobiotic metabolism. (1) Regulation of myelopoiesis is complex. As one example, AHR-mediated downregulation of human CD34+ progenitor differentiation to monocytes/macrophages is discussed. (2) Accumulation of TCDD in sebum leads to deregulation of sebocyte differentiation via Blimp1-mediated inhibition of c-Myc signaling and stimulation of Wnt-mediated proliferation of interfollicular epidermis. The resulting sebaceous gland atrophy and formation of dermal cysts may explain the pathogenesis of chloracne, the hallmark of TCDD toxicity. (3) TCDD treatment of confluent liver stem cell-like rat WB-F344 cells leads to release from cell-cell contact inhibition via AHR-mediated crosstalk with multiple signaling pathways. Further work is needed to delineate AHR function in crosstalk with other signaling pathways.
authors.affiliation: Department of Toxicology, Institute of Pharmacology and Toxicology, University of Tübingen, Tübingen, Germany. bock@uni-tuebingen.de.
authors.forename: Karl Walter
authors.initials: KW
authors.lastname: Bock
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000187:drug effects* / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D020239:Receptor Cross-Talk; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D012627:Sebaceous Glands / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon
keywords: Aryl hydrocarbon receptor; Chloracne; Signaling pathways; Stem/progenitor cells; TCDD toxicity