Morphine enhances Tat-induced activation in murine microglia

Sirosh M. Bokhari, Honghong Yao, Crystal Bethel-Brown, Peng Fuwang, Rachel Williams, Navneet K. Dhillon, Ramakrishna Hegde, Anil Kumar, Shilpa J. Buch

Research output: Contribution to journalArticlepeer-review

75 Scopus citations


There is increasing evidence that opiates accelerate the pathogenesis and progression of acquired immunodeficiency syndrome (AIDS), as well as the incidence of human immunodeficiency virus (HIV) encephalitis (HIVE), a condition characterized by inflammation, leukocyte infiltration, and microglial activation. The mechanisms, by which the HIV-1 transactivating protein Tat and opioids exacerbate microglial activation, however, are not fully understood. In the current study, we explored the effects of morphine and HIV-1 Tat172 on the activation of mouse BV-2 microglial cells and primary mouse microglia. Both morphine and Tat exposure caused up-regulation of the chemokine receptor CCR5, an effect blocked by the opioid receptor antagonist naltrexone. Morphine in combination with Tat also induced morphological changes in the BV-2 microglia from a quiescent to an activated morphology, with a dramatic increase in the expression of the microglial activation marker CD11b, as compared with cells exposed to either agent alone. In addition, the mRNA expression of inducible nitric oxide synthase (iNOS), CD40 ligand, Interferon-gamma-inducible protein 10 (IP-10), and the proinflammatory cytokines tumor necrosis factor alpha (TNF), interleukin (IL)-1, and IL-6, which were elevated with Tat alone, were dramatically enhanced with Tat in the presence of morphine. In summary, these findings shed light on the cooperative effects of morphine and HIV-1 Tat on both microglial activation and HIV coreceptor up-regulation, effects that could result in exacerbated neuropathogenesis.

Original languageEnglish (US)
Pages (from-to)219-228
Number of pages10
JournalJournal of neurovirology
Issue number3
StatePublished - 2009
Externally publishedYes


  • Activation
  • Cytokines
  • Microglia
  • Morphine
  • Tat

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology


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