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Regulation of mu-opioid receptor gene transcription by interleukin-4 and influence of an allelic variation within a STAT6 transcription factor binding site

Item Type:Article
Title:Regulation of mu-opioid receptor gene transcription by interleukin-4 and influence of an allelic variation within a STAT6 transcription factor binding site
Creators Name:Kraus, J. and Boerner, C. and Giannini, E. and Hickfang, K. and Braun, H. and Mayer, P. and Hoehe, M.R. and Ambrosch, A. and Koenig, W. and Hoelt, V.
Abstract:Morphine and the endogenous opioid peptide β-endorphin exert neuromodulatory as well as immunomodulatory effects, which are transduced by {my}-opioid receptors. In this report we show that stimulation with interleukin-4 induces μ-opioid receptor transcripts in human primary blood cells (T cells and polymorphonuclear leukocytes), immune cell lines (Raji, U-937, and HMEC-1), and dendritic cells. In nonstimulated immune cells this gene is silent. In addition, {my} receptor transcription is up-regulated by interleukin-4 in cultures of primary rat neurons. Transient transfection experiments in Raji and SH SY5Y neuronal cells with human and rat reporter gene constructs linked the interleukin-4 effect directly to cis-active {my} receptor promoter elements located at nucleotide -997 on the human gene and nucleotide -727 on the rat gene. The interleukin-4 response elements function orientation independently. They bind STAT6 transcription factors as shown by electrophoretic mobility shift assays. In the human gene, a single nucleotide polymorphism within the interleukin-4 response element reduces the trans-activating potential of this element by 50%, which may affect the phenotype of persons carrying this variation. These findings provide a molecular basis for understanding bidirectional interactions between the opioid system and the immune system.
Keywords:Alleles, Base Sequence, Binding Sites, Cell Line, Cerebral Cortex, DNA Primers, Genetic Transcription, Gene Expression Regulation, Interleukin-4, Mu Opioid Receptors, Neurons, Promoter Regions, Single Nucleotide Polymorphism, STAT6 Transcription Factor, Trans-Activators, Variation
Source:Journal of Biological Chemistry
ISSN:0021-9258
Publisher:American Society for Biochemistry and Molecular Biology (U.S.A.)
Volume:276
Number:47
Page Range:43901-43908
Date:1 January 2001
Official Publication:https://doi.org/10.1074/jbc.M107543200
PubMed:View item in PubMed

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