Dioxin-induced adseverin expression in the mouse thymus is strictly regulated and dependent on the aryl hydrocarbon receptor.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a ligand for the ubiquitous, intracellular aryl hydrocarbon receptor (AhR), up-regulates the actin-modulating protein adseverin in mouse lymphoid tissues, a response that may be correlated to the immunotoxicity of TCDD. Here, by using chimeric mice with TCDD-responsive (AhR(+/+)) hematopoietic cells and TCDD-unresponsive (AhR(minus sign/minus sign)) thymic stroma, or the reverse, we show that TCDD-induced expression of adseverin in thymus is dependent on AhR expression in hematopoietic cells but not in stroma. The use of fetal thymic organ cultures also indicates that TCDD-induced expression of adseverin is confined to the thymocytes. The thymic stroma showed no induction of adseverin expression after TCDD exposure, although TCDD clearly activated the AhR in these cells, as indicated by the induction of CYP1A1. Adseverin was not induced in the thymus of normal adult C57BL/6 mice exposed to beta-estradiol or dexamethasone, two other agents, which also cause thymic atrophy. This further supports that adseverin induction is a specific gene regulatory effect by TCDD on thymocytes.
Svensson
Camilla
C
Department of Pharmaceutical Biosciences, Division of Toxicology, P.O. Box 594, Uppsala University, E-751 24 Uppsala, Sweden. camilla.svensson@tox.uu.se
Silverstone
Allen E
AE
Lai
Zhi-Wei
ZW
Lundberg
Katarina
K
D000818:Animals; D001284:Atrophy / Q000378:metabolism; D018260:Gelsolin; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000096:biosynthesis* / Q000235:genetics; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology*; D017154:Stromal Cells / Q000187:drug effects / Q000502:physiology; D013723:Teratogens / Q000494:pharmacology; D013950:Thymus Gland / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D018260:Gelsolin; D008840:Microfilament Proteins; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D013723:Teratogens; C065395:scinderin