Limited role of COX-2 in HIV Tat-induced alterations of tight junction protein expression and disruption of the blood-brain barrier

Hong Pu, Kentaro Hayashi, Ibolya E. Andras, Sung Yong Eum, Bernhard Hennig, Michal Toborek

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Tat protein released from HIV-infected blood-borne leukocytes can contribute to the breakdown of the blood-brain barrier (BBB) and induction of inflammatory responses and can provide entry for HIV into the brain. To mimic this pathology, Tat was injected into the tail vein of C57BL/6 mice. Treatment with Tat markedly upregulated expression of cyclooxygenase-2 (COX-2) and decreased expression of tight junction proteins, occludin and zonula occludens-1 (ZO-1). These alterations were associated with the disruption of the BBB integrity as quantified by extravasation of Evans blue dye into the brain tissue. In addition, direct treatment of brain microvessels with prostaglandin E2, a product of COX-2 activity, resulted in decreased expression of both occludin and ZO-1. To determine if upregulation of COX-2 is involved in the disruption of tight junction proteins and BBB integrity, mice were pretreated with rofecoxib, a specific inhibitor of COX-2, prior to Tat treatment. COX-2 inhibition attenuated Tat-induced alterations of occludin expression. However, rofecoxib was ineffective in preventing downregulation of ZO-1 expression and increased BBB permeability. These results suggest only a limited role of COX-2 overexpression in the loss of tight junction integrity and the BBB breakdown in HIV-related brain diseases.

Original languageEnglish
Pages (from-to)333-344
Number of pages12
JournalBrain research
Volume1184
Issue number1
DOIs
Publication statusPublished - Dec 12 2007

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Keywords

  • Blood-brain barrier
  • Brain endothelium
  • HIV-1
  • HIV-associated dementia
  • Inflammation
  • Tat
  • Tight junction

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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