Morphine regulates gene expression of α- and β-chemokines and their receptors on astroglial cells via the opioid μ receptor Article

Mahajan, SD, Schwartz, SA, Shanahan, TC et al. (2002). Morphine regulates gene expression of α- and β-chemokines and their receptors on astroglial cells via the opioid μ receptor . JOURNAL OF IMMUNOLOGY, 169(7), 3589-3599. 10.4049/jimmunol.169.7.3589

cited authors

  • Mahajan, SD; Schwartz, SA; Shanahan, TC; Chawda, RP; Nair, MPN

authors

abstract

  • The brain is a target organ for recreational drugs and HIV-1. Epidemiological data demonstrate that opioid abuse is a risk factor for HIV-1 infection and progression to AIDS. Chemokines and their receptors have been implicated in the neuropathogenesis of HIV-1 infections. However, little is known about the effects of opioids on the expression of chemokines and their receptors (the latter also are HIV-1 coreceptors) by cells of the CNS. Herein we describe the effects of morphine on gene expression of the α- and β-chemokines and their receptors by the astrocytoma cell line U87 and by primary normal human astrocyte (NHA) cultures. U87 cells treated with morphine showed significant down-regulation of IL-8 gene expression, whereas expression of the IL-8 receptor CXCR2 was reciprocally up-regulated as detected by RT-PCR. Treatment of NHAs with morphine suppressed IL-8 and macrophage-inflammatory protein-1β gene expression, whereas expression of their receptor genes, CCR3 and CCR5, was simultaneously enhanced. These morphine-induced effects on U87 and NHA cells were reversed by the opioid μ receptor antagonist β-funaltrexamine. Morphine also enhanced the constitutive expression of the opioid μ receptor on astroglial cells. Our results support the hypothesis that opioids play a significant role in the susceptibility of the CNS to HIV-1 infection and subsequent encephalopathy by inhibiting local production of HIV-1-protective chemokines (IL-8 and macrophage-inflammatory protein-1β) and enhancing expression of HIV-1 entry coreceptor genes (CCR3, CCR5, and CXCR2) within the CNS. These effects of opioids appear to be mediated through the opioid μ receptor that we demonstrated on astroglial cells.

publication date

  • October 1, 2002

published in

Digital Object Identifier (DOI)

start page

  • 3589

end page

  • 3599

volume

  • 169

issue

  • 7