Morphine inhibits human microglial cell production of, and migration towards, RANTES.
The beta-chemokine RANTES has recently been implicated in the neuropathogenesis of the human immunodeficiency virus. Based upon previous studies of the effects of morphine on microglial cell production of cytokines and chemotaxis towards the activated complement component C5a, we tested the hypothesis that this opiate would alter the production of and migration towards RANTES by human microglia. Treatment of highly purified microglial cell cultures with morphine (10(-8)-10(-6) M) potently inhibited RANTES production by lipopolysaccharide- and interleukin-1beta-stimulated cells. Using a chemotaxis chamber to assess directed migration towards RANTES, treatment of microglial cells with morphine (10(-10)-10(-6) M) was found to suppress chemotaxis. The inhibitory effects of morphine on RANTES production and on chemotaxis were blocked by naloxone and beta-funaltrexamine, indicating that morphine mediated its suppressive effects via activation of microglial p-opioid receptors. Morphine's inhibitory effect on chemotaxis did not appear to be associated with an alteration in RANTES-induced [Ca2+]i mobilization. While the clinical significance of these in-vitro findings is unknown, they suggest that mu-opioid receptor agonists could alter certain neurodegenerative and inflammatory processes within the brain.
Hu
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Institute for Brain and Immune Disorders, Minneapolis Medical Research Foundation, Department of Medicine, Hennepin County Medical Centre, Minnesota 55404, USA.
Chao
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Hegg
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Thayer
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Peterson
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D001921:Brain / Q000166:cytology / Q000502:physiology; D002118:Calcium / Q000494:pharmacology / Q000502:physiology; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D005333:Fetus; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology
D018946:Chemokine CCL5; D007375:Interleukin-1; D008070:Lipopolysaccharides; D009292:Narcotic Antagonists; D011994:Recombinant Proteins; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D009271:Naltrexone; C024524:beta-funaltrexamine; D009020:Morphine; D002118:Calcium