Morphine modulates chemokine gene regulation in normal human astrocytes.
Chemokines and their receptors have been implicated in the pathogenesis of neuroAIDS. Herein we describe the effects of morphine on the gene expression of beta chemokines and their receptors by primary normal human astrocytes (NHA). Our results show that NHA treated with morphine showed significant downregulation of the gene expression of beta chemokines, MCP-1, and MIP-1 beta, while reciprocally upregulating the expression of their specific receptors, CCR2b, CCR3, and CCR5 as detected by real-time quantitative PCR. These morphine-induced effects on NHA cells were reversed by the opioid mu receptor antagonist, naloxone. Further, our results indicate that morphine-induced effects are mediated via the modulation of MAPK and CREB signaling pathways. These results support our hypothesis that opiates act as co-factors in the neuropathogenesis of HIV infection.
Mahajan
Supriya D
SD
Department of Medicine, Division of Allergy, Immunology, and Rheumatology, State University of New York and Buffalo General Hospital, 310 Multi Research Building, Kaleida Health, 100 High Street, Buffalo, NY 14203, USA.
Schwartz
Stanley A
SA
Aalinkeel
Ravikumar
R
Chawda
Ram P
RP
Sykes
Donald E
DE
Nair
Madhavan P N
MP
D001253:Astrocytes / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D054407:Chemokine CCL4; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D015536:Down-Regulation; D005786:Gene Expression Regulation; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000378:metabolism*; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D018932:Chemokine CCL2; D054407:Chemokine CCL4; D017362:Cyclic AMP Response Element-Binding Protein; D019402:Macrophage Inflammatory Proteins; D017450:Receptors, Opioid, mu; D009270:Naloxone; D009020:Morphine; D048051:p38 Mitogen-Activated Protein Kinases