Leukocyte activation induces aryl hydrocarbon receptor up-regulation, DNA binding, and increased Cyp1a1 expression in the absence of exogenous ligand.
The aryl hydrocarbon receptor (AhR) functions as a transcription factor after ligand binding by halogenated aromatic hydrocarbons. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic halogenated aromatic hydrocarbon, is dependent on binding to the AhR to mediate a broad range of toxic effects. Immune suppression is one of the most sensitive sequela associated with TCDD exposure, yet, paradoxically, resting leukocytes express a relatively low amount of AhR. Here we report that activation of leukocytes produced a 6-fold increase in AhR steady state mRNA levels and a concordant increase in AhR protein expression. Furthermore, leukocyte activation induced AhR translocation, DNA binding to a dioxin response element, and CYP1A1 transcription in the absence of TCDD. Activated leukocytes exhibited an even greater enhancement of dioxin response element binding by the AhR in the presence of TCDD than in the absence of TCDD. These studies suggest that the mechanism responsible for the sensitivity of immunocompetent cells to TCDD may be directly associated with a marked increase in AhR expression, which accompanies leukocyte activation.[1]References
- Leukocyte activation induces aryl hydrocarbon receptor up-regulation, DNA binding, and increased Cyp1a1 expression in the absence of exogenous ligand. Crawford, R.B., Holsapple, M.P., Kaminski, N.E. Mol. Pharmacol. (1997) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
