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Research ArticleArticle

Immune-Specific Up-Regulation of Adseverin Gene Expression by 2,3,7,8-Tetrachlorodibenzo-p-dioxin

Camilla Svensson and Katarina Lundberg
Molecular Pharmacology July 2001, 60 (1) 135-142; DOI: https://doi.org/10.1124/mol.60.1.135
Camilla Svensson
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Katarina Lundberg
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Abstract

To identify genes that are regulated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and possibly involved in TCDD-induced immunotoxicity, we used the differential display technique to screen for differentially expressed genes in the mouse thymus. Here we show that TCDD increased the expression of adseverin, a Ca2+-dependent, actin-severing protein. The induction of adseverin is dose- and time-dependent in parallel with the induction of CYP1A1, which is currently the most frequently used marker for TCDD exposure. A comparison between mouse strains with different TCDD responsiveness indicated that the induction of adseverin is dependent on the aryl hydrocarbon receptor, a transcription factor known to mediate most of TCDD's biological effects. Examination of additional organs revealed that the up-regulation of the adseverin gene expression is immune-specific. Using an anti-adseverin antibody, we confirmed the induction of adseverin by TCDD at the protein level and it was confined to the thymic cortex, which harbors immature thymocytes that are known target cells of TCDD. Considering adseverin's role in actin cytoskeletal reorganization, our observations reveal new mechanistic aspects of how TCDD might exert some of its immunotoxic effects.

  • Abbreviations

    TCDD
    2,3,7,8-tetrachlorodibenzo-p-dioxin
    AhR
    aryl hydrocarbon receptor
    PBS
    phosphate-buffered saline
    FCS
    fetal calf serum
    IL
    interleukin
    RT
    reverse transcription
    PCR
    polymerase chain reaction
    HPRT
    hypoxanthine phosphoribosyl nucleotide transferase
    ab
    antibody
    differential display
    differential display RT-PCR
    bp
    base pair(s)
    PIP2
    phosphatidylinositol 4,5-bisphosphate
    PLCγ
    phospholipase Cγ
    • Received December 28, 2000.
    • Accepted March 21, 2001.
    • The American Society for Pharmacology and Experimental Therapeutics
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    Molecular Pharmacology: 60 (1)
    Molecular Pharmacology
    Vol. 60, Issue 1
    1 Jul 2001
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    Research ArticleArticle

    Immune-Specific Up-Regulation of Adseverin Gene Expression by 2,3,7,8-Tetrachlorodibenzo-p-dioxin

    Camilla Svensson and Katarina Lundberg
    Molecular Pharmacology July 1, 2001, 60 (1) 135-142; DOI: https://doi.org/10.1124/mol.60.1.135

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    Research ArticleArticle

    Immune-Specific Up-Regulation of Adseverin Gene Expression by 2,3,7,8-Tetrachlorodibenzo-p-dioxin

    Camilla Svensson and Katarina Lundberg
    Molecular Pharmacology July 1, 2001, 60 (1) 135-142; DOI: https://doi.org/10.1124/mol.60.1.135
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