Synergistic increases in intracellular Ca2+, and the release of MCP-1, RANTES, and IL-6 by astrocytes treated with opiates and HIV-1 tat Article

El-Hage, N, Gurwell, JA, Singh, IN et al. (2005). Synergistic increases in intracellular Ca2+, and the release of MCP-1, RANTES, and IL-6 by astrocytes treated with opiates and HIV-1 tat . GLIA, 50(2), 91-106. 10.1002/glia.20148

cited authors

  • El-Hage, N; Gurwell, JA; Singh, IN; Knapp, PE; Nath, A; Hauser, KF

authors

abstract

  • Recent evidence suggests that injection drug users who abuse heroin are at increased risk of CNS complications from human immunodeficiency virus (HIV) infection. Opiate drugs may intrinsically alter the pathogenesis of HIV by directly modulating immune function and by directly modifying the CNS response to HIV. Despite this, the mechanisms by which opiates increase the neuropathogenesis of HIV are uncertain. In the present study, we describe the effect of morphine and the HIV-1 protein toxin Tat1-72 on astroglial function in cultures derived from ICR mice. Astroglia maintain the blood-brain barrier and influence inflammatory signaling in the CNS. Astrocytes can express μ-opioid receptors, and are likely targets for abused opiates, which preferentially activate μ-opioid receptors. While Tat alone disrupts astrocyte function, when combined with morphine, Tat causes synergistic increases in [Ca2+]i. Moreover, astrocyte cultures treated with morphine and Tat showed exaggerated increases in chemokine release, including monocyte chemoattractant protein-1 (MCP-1) and regulated on activation, normal T cell expressed and secreted (RANTES), as well as interleukin-6 (IL-6). Morphine-Tat interactions were prevented by the μ-opioid receptor antagonist β-funaltrexamine, or by immunoneutralizing Tat1-72 or substituting a nontoxic, deletion mutant (Tat Δ31-61). Our findings suggest that opiates may increase the vulnerability of the CNS to viral entry (via recruitment of monocytes/ macrophages) and ensuing HIV encephalitis by synergistically increasing MCP-1 and RANTES release by astrocytes. The results further suggest that astrocytes are key intermediaries in opiate-HIV interactions and disruptions in astroglial function and inflammatory signaling may contribute to an accelerated neuropathogenesis in HIV-infected individuals who abuse opiates. © 2005 Wiley-Liss, Inc.

publication date

  • April 15, 2005

published in

Digital Object Identifier (DOI)

start page

  • 91

end page

  • 106

volume

  • 50

issue

  • 2