Morphine exacerbates HIV-1 viral protein gp120 induced modulation of chemokine gene expression in U373 astrocytoma cells.
HIV-1 affects microglia and astroglia, which subsequently contributes to the neurodegenerative changes. Viral proteins cause neurotoxicity by direct action on the CNS cells or by activating glial cells to cause the release of cytokines, chemokines or neurotoxic substances. Opioid abuse has been postulated as a cofactor in the immunopathogenesis of human immunodeficiency virus (HIV) infection and AIDS. HIV-induced pathogenesis is exacerbated by opiate abuse and that the synergistic neurotoxicity is a direct effect of opiates on the CNS. Chemokines and their receptors have been implicated in the pathogenesis of neuroAIDS. Herein we describe the effects of morphine and/or gp120 on the expression of the genes for the beta-chemokine MIP-1beta and its receptors CCR3 and CCR5 by the U373 cells which are a human brain-derived astrocytoma/glioblastoma cell line. Our results indicate that treatment of U373 cells with morphine significantly downregulated the gene expression of the beta chemokine, MIP-1 beta, while reciprocally upregulating the expression of its specific receptors, CCR3 and CCR5 suggesting that the capacity of mu-opioids to increase HIV-1 co-receptor expression may promote viral binding, trafficking of HIV-1-infected cells, and enhanced disease progression. Additionally, opiates can enhance the cytotoxicity of HIV-1 viral protein gp120 via mechanisms that involve intracellular calcium modulation resulting in direct actions on astroglia, making them an important cellular target for HIV-opiate interactions.
Mahajan
Supriya D
SD
Department of Medicine, Division of Allergy, Immunology, and Rheumatology, State University of New York and Buffalo General Hospital, Kaleida Health, 100 High Street, Buffalo, NY 14203, USA.
Aalinkeel
Ravikumar
R
Reynolds
Jessica L
JL
Nair
Bindukumar B
BB
Fernandez
Stanley F
SF
Schwartz
Stanley A
SA
Nair
Madhavan P N
MP
D015526:AIDS Dementia Complex / Q000209:etiology / Q000235:genetics / Q000276:immunology; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D054407:Chemokine CCL4; D018925:Chemokines / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects; D015699:HIV Envelope Protein gp120 / Q000276:immunology* / Q000633:toxicity*; D015658:HIV Infections / Q000209:etiology / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D066298:In Vitro Techniques; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000235:genetics; D009020:Morphine / Q000633:toxicity*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D054397:Receptors, CCR3; D019713:Receptors, CCR5 / Q000096:biosynthesis / Q000235:genetics; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000235:genetics; D017450:Receptors, Opioid, mu / Q000096:biosynthesis / Q000187:drug effects
C515350:CCR3 protein, human; D054407:Chemokine CCL4; D018925:Chemokines; D015699:HIV Envelope Protein gp120; D007155:Immunologic Factors; D019402:Macrophage Inflammatory Proteins; D009292:Narcotic Antagonists; D054397:Receptors, CCR3; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D017450:Receptors, Opioid, mu; D009270:Naloxone; D009020:Morphine; D002118:Calcium