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

Nazira El-Hage, Elizabeth M. Podhaizer, Jamie Sturgill, Kurt F. Hauser

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

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.

Original languageEnglish
Pages (from-to)498-522
Number of pages25
JournalImmunological Investigations
Volume40
Issue number5
DOIs
StatePublished - 2011

Bibliographical note

Funding Information:
We thank Drs. Seth M. Dever and Krista Scoggins for editing the manuscript. This work was supported by grants AD Williams (NE), and R03 DA026744-01 (NE), P01 DA19298, (KH), K02 DA027374 (KH), and T32 DA007027 (EP) from the NIH/NIDA. Flow cytometry was supported in part by NIH grant P30CA16059.

Keywords

  • Cytokines
  • Free radicals
  • Glia
  • HIV-1 proteins
  • Innate immunity
  • Neuroplasticity
  • Opioid abuse

ASJC Scopus subject areas

  • Immunology

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