HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/4/H2210    most recent 00688.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (28) Citing Articles via Google Scholar Google Scholar Articles by Rajesh, M. Articles by Pacher, P. Search for Related Content PubMed PubMed Citation Articles by Rajesh, M. Articles by Pacher, P.

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

¹Section on Oxidative Stress Tissue Injury, Laboratory of Physiological Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland; ²Department of Surgery, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey; ³Department of Intensive Care Medicine, University Hospital, Lausanne, Switzerland; ⁴Howard L. Hunter Chemistry Laboratory, Clemson University, South Carolina; ⁵Department of Physiology, New York Medical College, Valhalla, New York; ⁶Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana; and ⁷Department of Pediatrics, Lipid Research Unit, Johns Hopkins University, Baltimore, Maryland

Submitted 13 June 2007 ; accepted in final form 26 July 2007

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--induced signal transduction in human coronary artery endothelial cells in vitro and on endotoxin-induced vascular inflammatory response in vivo. TNF- induced NF-B 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- were attenuated by CB₂ agonists. CB₂ agonists also decreased the TNF-- 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--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.

endothelial activation; inflammation; RhoA; adhesion molecules

This article has been cited by other articles:

				K. H. Han, S. Lim, J. Ryu, C.-W. Lee, Y. Kim, J.-H. Kang, S.-S. Kang, Y. K. Ahn, C.-S. Park, and J. J. Kim CB1 and CB2 cannabinoid receptors differentially regulate the production of reactive oxygen species by macrophages Cardiovasc Res, December 1, 2009; 84(3): 378 - 386. [Abstract] [Full Text] [PDF]

				N. Defer, J. Wan, R. Souktani, B. Escoubet, M. Perier, P. Caramelle, S. Manin, V. Deveaux, M.-C. Bourin, A. Zimmer, et al. The cannabinoid receptor type 2 promotes cardiac myocyte and fibroblast survival and protects against ischemia/reperfusion-induced cardiomyopathy FASEB J, July 1, 2009; 23(7): 2120 - 2130. [Abstract] [Full Text] [PDF]

				A. G. Rajapakse, X.-F. Ming, J. M. Carvas, and Z. Yang The hexosamine biosynthesis inhibitor azaserine prevents endothelial inflammation and dysfunction under hyperglycemic condition through antioxidant effects Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H815 - H822. [Abstract] [Full Text] [PDF]

				P. Pacher Cannabinoid CB1 Receptor Antagonists for Atherosclerosis and Cardiometabolic Disorders: New Hopes, Old Concerns? Arterioscler Thromb Vasc Biol, January 1, 2009; 29(1): 7 - 9. [Full Text] [PDF]

				F. Dol-Gleizes, R. Paumelle, V. Visentin, A.-M. Mares, P. Desitter, N. Hennuyer, A. Gilde, B. Staels, P. Schaeffer, and F. Bono Rimonabant, a Selective Cannabinoid CB1 Receptor Antagonist, Inhibits Atherosclerosis in LDL Receptor-Deficient Mice Arterioscler Thromb Vasc Biol, January 1, 2009; 29(1): 12 - 18. [Abstract] [Full Text] [PDF]

				M. Iribarne, V. Torbidoni, K. Julian, J. P. Prestifilippo, D. Sinha, V. Rettori, A. Berra, and A. M. Suburo Cannabinoid Receptors in Conjunctival Epithelium: Identification and Functional Properties Invest. Ophthalmol. Vis. Sci., October 1, 2008; 49(10): 4535 - 4544. [Abstract] [Full Text] [PDF]

				P. Pacher, P. Mukhopadhyay, R. Mohanraj, G. Godlewski, S. Batkai, and G. Kunos Modulation of the Endocannabinoid System in Cardiovascular Disease: Therapeutic Potential and Limitations Hypertension, October 1, 2008; 52(4): 601 - 607. [Full Text] [PDF]

				P. Pacher and B. Gao Endocannabinoids and Liver Disease. III. Endocannabinoid effects on immune cells: implications for inflammatory liver diseases Am J Physiol Gastrointest Liver Physiol, April 1, 2008; 294(4): G850 - G854. [Abstract] [Full Text] [PDF]

				F. Montecucco, F. Burger, F. Mach, and S. Steffens CB2 cannabinoid receptor agonist JWH-015 modulates human monocyte migration through defined intracellular signaling pathways Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1145 - H1155. [Abstract] [Full Text] [PDF]

				P. Pacher and Z. Ungvari Pleiotropic effects of the CB2 cannabinoid receptor activation on human monocyte migration: implications for atherosclerosis and inflammatory diseases Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1133 - H1134. [Full Text] [PDF]