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Blood. 2011 Feb 24;117(8):2538-47. doi: 10.1182/blood-2010-10-313593. Epub 2010 Dec 8.

Cocaine-mediated induction of platelet-derived growth factor: implication for increased vascular permeability.

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1
Department of Pharmacology and Experimental Neuroscience, 985880 Nebraska MedicalCenter, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.

Erratum in

  • Blood. 2015 Jun 11;125(24):3823.

Abstract

Neuroinflammation associated with advanced HIV-1 infection is often exacerbated in cocaine-abusing, HIV-infected patients. The underlying mechanisms could, in part, be attributed to the increased impairment of blood brain barrier integrity in the presence of cocaine. Platelet-derived growth factor (PDGF) has been implicated in several pathologic conditions, specifically attributable to its potent mitogenic effects. Its modulation by drug abuse, however, has received very little attention. In the present study, we demonstrated cocaine-mediated induction of PDGF-BB in human brain microvascular endothelial cells through the binding to its cognate σ receptor. Furthermore, this effect was mediated, with subsequent activation of mitogen-activated protein kinases and Egr-1 pathways, culminating ultimately into increased expression of PDGF-BB. Cocaine exposure resulted in increased permeability of the endothelial barrier, and this effect was abrogated in mice exposed to PDGF-BB neutralizing antibody, thus underscoring its role as a vascular permeant. In vivo relevance of these findings was further corroborated in cocaine-treated mice that were administered neutralizing antibody specific for PDGF-BB as well as in Egr-1(-/-) mice. Understanding the regulation of PDGF-BB expression may provide insights into the development of potential therapeutic targets for neuroinflammation associated with HIV infection and drug abuse.

Comment in

PMID:
21148086
PMCID:
PMC3062415
DOI:
10.1182/blood-2010-10-313593
[Indexed for MEDLINE]
Free PMC Article
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