Toll-like receptor expression and activation in astroglia: Differential regulation by HIV-1 Tat, gp120, and morphine Article

El-Hage, N, Podhaizer, EM, Sturgill, J et al. (2011). Toll-like receptor expression and activation in astroglia: Differential regulation by HIV-1 Tat, gp120, and morphine . 40(5), 498-522. 10.3109/08820139.2011.561904

cited authors

  • El-Hage, N; Podhaizer, EM; Sturgill, J; Hauser, KF

authors

abstract

  • In this study, we aimed to determine whether morphine alone or in combination with HIV-1 Tat or gp120 affects the expression of Toll-like receptors (TLRs) by astrocytes and to assess whether TLRs expressed by astrocytes function in the release of inflammatory mediators in vitro. TLR profiling by immunofluorescence microscopy, flow cytometry, in-cell westerns, and RT-PCR showed that subpopulations of astrocytes possessed TLR 2, TLR3, TLR4, and TLR9 antigenicity. Exposure to HIV-1 Tat, gp120, and/or morphine significantly altered the proportion of TLR-immunopositive and/or TLR expression by astroglia in a TLR-specific manner. Subsets of astroglia displayed significant increases in TLR2 with reciprocal decreases in TLR9 expression in response to Tat or gp120 ± morphine treatment. TLR9 expression was also significantly decreased by morphine alone. Exposing astrocytes to the TLR agonists LTA (TLR2), poly I:C (TLR3), LPS (TLR4) and unmethylated CpG ODN (TLR9) resulted in increased secretion of MCP-1/CCL2 and elevations in reactive oxygen species. TLR3 and TLR4 stimulation increased the secretion of TNF-α, IL-6, and RANTES/CCL5, while activation of TLR2 caused a significant increase in nitric oxide levels. The results suggest that HIV-1 proteins and/or opioid abuse disrupt the innate immune response of the central nervous system (CNS) which may lead to increased pathogenicity. © 2011 Informa Healthcare USA, Inc.

publication date

  • December 1, 2011

Digital Object Identifier (DOI)

start page

  • 498

end page

  • 522

volume

  • 40

issue

  • 5