Cyclooxygenase-2 is involved in HIV-1 Tat-induced inflammatory responses in the brain

Govinder Flora, Hong Pu, Bernhard Hennig, Michal J Toborek

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Cyclooxygenase (COX)-2, a rate-limiting enzyme for prostanoid synthesis, can be involved in inflammatory-mediated cytotoxicity. Although the contribution of COX-2 to peripheral inflammation is well understood, its role in brain inflammation is not fully recognized. In particular, COX-2 involvement in inflammatory responses induced by HIV proteins in the central nervous system is not known. Therefore, the present study focused on COX-2 expression and its role in modulating the expression of brain inflammatory-related genes following exposure to the HIV-1 transactivating protein Tat. Intrahippocampal injections of Tat induced dose-dependent upregulation of COX-2 mRNA and protein levels in C57BL/6 mice. COX-2 immunoreactivity was primarily localized in microglial cells and astrocytes. Tat-induced COX-2 expression was partially prevented by pyrrolidine dithiocarbamate, a potent antioxidant and an inhibitor of the transcription factor, nuclear factor κB. Most importantly, administration of the COX-2 inhibitor NS-398 attenuated Tat-mediated upregulation of mRNAand protein expression of inflammatory mediators, such as monocyte chemoattractant protein-1, interleukin-1Β, tumor necrosis factor-α, and inducible nitric oxide synthase. Moreover, treatment with NS-398 significantly attenuated Tatinduced activation of microglial cells. These results provide evidence that COX-2 overexpression can modulate induction of brain inflammatory mediators in response to HIV-1 Tat protein. Such alterations may play an important role in the development of brain inflammatory reactions in HIV-infected patients and contribute to the development of neurological complications in the course of HIV-1 infection.

Original languageEnglish
Pages (from-to)337-352
Number of pages16
JournalNeuroMolecular Medicine
Volume8
Issue number3
DOIs
StatePublished - Sep 1 2006
Externally publishedYes

Fingerprint

Cyclooxygenase 2
HIV-1
Brain
Up-Regulation
Human Immunodeficiency Virus tat Gene Products
tat Gene Products
Human Immunodeficiency Virus Proteins
Chemokine CCL2
Cyclooxygenase 2 Inhibitors
Nitric Oxide Synthase Type II
Encephalitis
Interleukin-1
Inbred C57BL Mouse
Astrocytes
HIV Infections
Prostaglandins
Proteins
Transcription Factors
Central Nervous System
Tumor Necrosis Factor-alpha

Keywords

  • CNS
  • COX
  • HIV-1
  • HIV-associated dementia
  • Inflammation
  • NF-κB
  • Tat

ASJC Scopus subject areas

  • Neuroscience(all)
  • Genetics
  • Cell Biology

Cite this

Cyclooxygenase-2 is involved in HIV-1 Tat-induced inflammatory responses in the brain. / Flora, Govinder; Pu, Hong; Hennig, Bernhard; Toborek, Michal J.

In: NeuroMolecular Medicine, Vol. 8, No. 3, 01.09.2006, p. 337-352.

Research output: Contribution to journalArticle

Flora, Govinder ; Pu, Hong ; Hennig, Bernhard ; Toborek, Michal J. / Cyclooxygenase-2 is involved in HIV-1 Tat-induced inflammatory responses in the brain. In: NeuroMolecular Medicine. 2006 ; Vol. 8, No. 3. pp. 337-352.
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