Epigenetic mechanisms involved in the induction of the mu opioid receptor gene in Jurkat T cells in response to interleukin-4.

Jürgen Kraus, Lienhard Lehmann, Christine Börner, Volker Höllt

Department of Pharmacology and Toxicology, University of Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany. juergen.kraus@med.ovgu.de

Molecular immunology 2010 Nov-Dec

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Various immunomodulatory effects of opioids are mediated by mu opioid receptors. While in resting T lymphocytes their expression is repressed, mu opioid receptors are induced by interleukin-4 via the transcription factor STAT6. Here we investigated mechanisms underlying this induction in human Jurkat T cells. Although interleukin-4 induced a rapid activation of STAT6 by phosphorylation within few minutes, chromatin-immune-precipitation analysis revealed that the binding of STAT6 to its regulatory DNA element on the mu opioid receptor promoter occurs later than 2h after interleukin-4-stimulation. Detectable amounts of the mu opioid receptor mRNA were observed later than 3h after stimulation. Preceding the binding of STAT6, several epigenetic mechanisms were observed that are known to modify the chromatin architecture of a gene. Thus, we detected by chromatin-immune-precipitation analysis transient association of the mu opioid receptor gene promoter with trimethylated histone H3 at lysine 4, phosphorylated (serine 10) plus acetylated (lysine 14) histone H3, and acetylated histone H4 at lysine 16. In addition, binding of the methyl-cytosine-guanine dinucleotide-binding protein MeCP2 to the mu opioid receptor promoter decreased during the interleukin-4 treatment of Jurkat cells. Furthermore, we detected a transient association of the mu opioid receptor promoter with Brg-1, which is a protein contained in ATP-dependent chromatin remodeling complexes and known to facilitate transcriptional activation of a gene. Together, these data suggest that epigenetic modifications of the chromatin of the mu opioid receptor gene are involved in the transcriptional activation of the gene in response to interleukin-4 in T cells. Copyright © 2010 Elsevier Ltd. All rights reserved.

Citation

Jürgen Kraus, Lienhard Lehmann, Christine Börner, Volker Höllt. Epigenetic mechanisms involved in the induction of the mu opioid receptor gene in Jurkat T cells in response to interleukin-4. Molecular immunology. 2010 Nov-Dec;48(1-3):257-63