Cocaine-mediated alteration in tight junction protein expression and modulation of CCL2/CCR2 axis across the blood-brain barrier: Implications for HIV-dementia

Navneet K. Dhillon, Fuwang Peng, Sirosh Bokhari, Shannon Callen, Sun Hye Shin, Xuhui Zhu, Kee Jun Kim, Shilpa J. Buch

Research output: Contribution to journalArticle

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Abstract

One of the hallmark features underlying the pathogenesis of HIV encephalitis is the disruption of blood-brain barrier (BBB). Cocaine, often abused by HIV-infected patients, has been suggested to worsen the HIV-associated dementia (HAD) via unknown mechanisms. The objective of the present study was to explore the effects of cocaine on BBB permeability using human brain microvascular endothelial cells (HBMECs). Additionally, because the chemokine CCL2 and its receptor CCR2 play a crucial role in the recruitment of inflammatory cells into the central nervous system in HAD brains, we tested for the effect of cocaine in modulating the CCL2/CCR2 axis. Our findings suggest that exposure of HBMECs to cocaine correlated with the breakdown of ZO-1 tight junction protein and reorganization of the cytoskeleton resulting in stress fiber formation. Furthermore, cocaine also modulated upregulation of the CCL2/CCR2 axis in monocytes. These findings conform to the multifaceted effects of cocaine leading to accelerated progression of HIV-1 neuropathogenesis.

Original languageEnglish (US)
Pages (from-to)52-56
Number of pages5
JournalJournal of Neuroimmune Pharmacology
Volume3
Issue number1
DOIs
StatePublished - Mar 1 2008

Fingerprint

AIDS Dementia Complex
Tight Junction Proteins
Blood-Brain Barrier
Cocaine
Brain
Endothelial Cells
CCR2 Receptors
Zonula Occludens-1 Protein
HIV
Stress Fibers
Chemokine CCL2
Encephalitis
Cytoskeleton
HIV-1
Monocytes
Permeability
Up-Regulation
Central Nervous System

Keywords

  • Blood-brain barrier
  • CCL2
  • Cocaine
  • HIV

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

Cocaine-mediated alteration in tight junction protein expression and modulation of CCL2/CCR2 axis across the blood-brain barrier : Implications for HIV-dementia. / Dhillon, Navneet K.; Peng, Fuwang; Bokhari, Sirosh; Callen, Shannon; Shin, Sun Hye; Zhu, Xuhui; Kim, Kee Jun; Buch, Shilpa J.

In: Journal of Neuroimmune Pharmacology, Vol. 3, No. 1, 01.03.2008, p. 52-56.

Research output: Contribution to journalArticle

Dhillon, Navneet K. ; Peng, Fuwang ; Bokhari, Sirosh ; Callen, Shannon ; Shin, Sun Hye ; Zhu, Xuhui ; Kim, Kee Jun ; Buch, Shilpa J. / Cocaine-mediated alteration in tight junction protein expression and modulation of CCL2/CCR2 axis across the blood-brain barrier : Implications for HIV-dementia. In: Journal of Neuroimmune Pharmacology. 2008 ; Vol. 3, No. 1. pp. 52-56.
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