CB2-receptor stimulation attenuates TNF-α-induced human endothelial cell activation, transendothelial migration of monocytes, and monocyte-endothelial adhesion

Mohanraj Rajesh, Partha Mukhopadhyay, Sándor Bátkai, György Haskó, Lucas Liaudet, John W. Huffman, Anna Csiszar, Zoltan Ungvari, Ken Mackie, Subroto Chatterjee, Pál Pacher

Research output: Contribution to journalArticle

Abstract

Targeting cannabinoid-2 (CB2) receptors with selective agonists may represent a novel therapeutic avenue in various inflammatory diseases, but the mechanisms by which CB2 activation exerts its anti-inflammatory effects and the cellular targets are elusive. Here, we investigated the effects of CB2-receptor activation on TNF-α-induced signal transduction in human coronary artery endothelial cells in vitro and on endotoxin-induced vascular inflammatory response in vivo. TNF-α induced NF-κB and RhoA activation and upregulation of adhesion molecules ICAM-1 and VCAM-1, increased expression of monocyte chemoattractant protein, enhanced transendothelial migration of monocytes, and augmented monocyte-endothelial adhesion. Remarkably, all of the above-mentioned effects of TNF-α were attenuated by CB 2 agonists. CB2 agonists also decreased the TNF-α- and/or endotoxin-induced ICAM-1 and VCAM-1 expression in isolated aortas and the adhesion of monocytes to aortic vascular endothelium. CB1 and CB2 receptors were detectable in human coronary artery endothelial cells by Western blotting, RT-PCR, real-time PCR, and immunofluorescence staining. Because the above-mentioned TNF-α-induced phenotypic changes are critical in the initiation and progression of atherosclerosis and restenosis, our findings suggest that targeting CB2 receptors on endothelial cells may offer a novel approach in the treatment of these pathologies.

Original languageEnglish (US)
Pages (from-to)H2210-H2218
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume293
Issue number4
DOIs
StatePublished - Oct 1 2007

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Keywords

  • Adhesion molecules
  • Endothelial activation
  • Inflammation
  • RhoA

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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