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Rapid CommunicationAccelerated Communication

Leukocyte Activation Induces Aryl Hydrocarbon Receptor Up-Regulation, DNA Binding, and Increased Cyp1a1Expression in the Absence of Exogenous Ligand

Robert B. Crawford, Michael P. Holsapple and Norbert E. Kaminski
Molecular Pharmacology December 1997, 52 (6) 921-927; DOI: https://doi.org/10.1124/mol.52.6.921
Robert B. Crawford
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Michael P. Holsapple
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Norbert E. Kaminski
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Abstract

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.

Footnotes

    • Received July 25, 1997.
    • Accepted September 9, 1997.
  • Send reprint requests to: Dr. Norbert E. Kaminski, Dept. of Pharmacology and Toxicology, B-330 Life Sciences Bldg., Michigan State University, East Lansing, Michigan 48824. E-mail:kamins11{at}gems.msu.edu

  • This work was supported in part by National Institutes of Health Grant ES02520.

  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 52 (6)
Molecular Pharmacology
Vol. 52, Issue 6
1 Dec 1997
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Rapid CommunicationAccelerated Communication

Leukocyte Activation Induces Aryl Hydrocarbon Receptor Up-Regulation, DNA Binding, and Increased Cyp1a1Expression in the Absence of Exogenous Ligand

Robert B. Crawford, Michael P. Holsapple and Norbert E. Kaminski
Molecular Pharmacology December 1, 1997, 52 (6) 921-927; DOI: https://doi.org/10.1124/mol.52.6.921

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Rapid CommunicationAccelerated Communication

Leukocyte Activation Induces Aryl Hydrocarbon Receptor Up-Regulation, DNA Binding, and Increased Cyp1a1Expression in the Absence of Exogenous Ligand

Robert B. Crawford, Michael P. Holsapple and Norbert E. Kaminski
Molecular Pharmacology December 1, 1997, 52 (6) 921-927; DOI: https://doi.org/10.1124/mol.52.6.921
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