Interleukin-1 beta-mediated regulation of mu-opioid receptor mRNA in primary astrocyte-enriched cultures.
Opioids have been found to modulate the immune system by regulating the function of immunocompetent cells. Several studies suggest that the interaction between immune and opioid systems is not unidirectional, but rather reciprocal, in nature. In the CNS, one cellular target of immune system activation is the astrocytes. These glial cells have been shown to produce the opioid peptide, proenkephalin, to express the mu-, delta-, and kappa-opioid receptors, and to respond to the immune factor interleukin-1 beta (IL1 beta) with an increased proenkephalin synthesis. To characterize more completely the astrocytic opioid response to immune factor stimulation, we examined the effect of IL1 beta (1 ng/ml) on the mu-receptor mRNA expression in primary astrocyte-enriched cultures derived from rat (postnatal day 1-2) cortex, striatum, cerebellum, hippocampus, and hypothalamus. A 24-h treatment with IL1 beta produced a 70-80% increase in the mu-receptor mRNA expression in the striatal, cerebellar, and hippocampal cultures but had no effect on this expression in the cortical and hypothalamic cultures. This observation represents one of the few demonstrated increases in levels of the mu-receptor mRNA in vitro or in vivo, since the cloning of the receptor. The enhanced mu-receptor mRNA expression, together with the previous observation that IL1 beta stimulates proenkephalin synthesis in astrocytes, supports the IL1 beta-mediated regulation of an astroglial opioid peptide and receptor in vitro, a phenomenon that may be significant in the modulation of the gliotic response to neuronal damage. Therefore, the astroglial opioid "system" may be important in the IL1 beta-initiated, coordinated response to CNS infection, trauma, or injury.
Mental Health Research Institute, University of Michigan, Ann Arbor 48109-0720, USA.
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Ruzicka
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Thompson
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SJ
Watson
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H
Akil
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000033:anatomy & histology / Q000166:cytology; D002478:Cells, Cultured; D004745:Enkephalins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D007375:Interleukin-1 / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009928:Organ Specificity; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017450:Receptors, Opioid, mu / Q000096:biosynthesis* / Q000235:genetics
D004745:Enkephalins; D007375:Interleukin-1; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D017450:Receptors, Opioid, mu; C029992:proenkephalin