Morphine Exacerbates HIV-1 Viral Protein gp120 Induced Modulation of Chemokine Gene Expression in U373 Astrocytoma Cells

Author(s): Supriya D. Mahajan, Ravikumar Aalinkeel, Jessica L. Reynolds, Bindukumar B. Nair, Stanley F. Fernandez, Stanley A. Schwartz, Madhavan P.N. Nair.

Journal Name: Current HIV Research

Volume 3 , Issue 3 , 2005

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Abstract:

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 βchemokine MIP-1β 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 β chemokine, MIPβ1 β, 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.

Keywords: morphine, astroglia, hiv, gp, chemokines

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Article Details

VOLUME: 3
ISSUE: 3
Year: 2005
Page: [277 - 288]
Pages: 12
DOI: 10.2174/1570162054368048
Price: $58

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