FASEB J.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (Rapid PDF)
Right arrow All Versions of this Article:
fj.06-7451comv1
fj.06-7451comv2
21/8/1788    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bátkai, S.
Right arrow Articles by Pacher, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bátkai, S.
Right arrow Articles by Pacher, P.
Published online before print March 7, 2007 as doi: 10.1096/fj.06-7451com.

Cannabinoid-2 receptor mediates protection against hepatic ischemia/reperfusion injury

Sándor Bátkai, Douglas Osei-Hyiaman, Hao Pan, Osama El-Assal, Mohanraj Rajesh, Partha Mukhopadhyay, Feng Hong, Judith Harvey-White, Anjum Jafri, György Haskó, John W. Huffman, Bin Gao, George Kunos, and Pál Pacher

E-mail contact: pacher@mail.nih.gov

Hepatic ischemia-reperfusion (I/R) injury continues to be a fatal complication that can follow liver surgery or transplantation. We have investigated the involvement of the endocannabinoid system in hepatic I/R injury using an in vivo mouse model. Here we report that I/R triggers several-fold increases in the hepatic levels of the endocannabinoids anandamide and 2-arachidonoylglycerol, which originate from hepatocytes, Kupffer, and endothelial cells. The I/R-induced increased tissue endocannabinoid levels positively correlate with the degree of hepatic damage and serum TNF-{alpha}, MIP-1{alpha}, and MIP-2 levels. Furthermore, a brief exposure of hepatocytes to various oxidants (H2O2 and peroxynitrite) or inflammatory stimuli (endotoxin and TNF-{alpha}) also increases endocannabinoid levels. Activation of CB2 cannabinoid receptors by JWH133 protects against I/R damage by decreasing inflammatory cell infiltration, tissue and serum TNF-{alpha}, MIP-1{alpha} and MIP-2 levels, tissue lipid peroxidation, and expression of adhesion molecule ICAM-1 in vivo. JWH133 also attenuates the TNF-{alpha}-induced ICAM-1 and VCAM-1 expression in human liver sinusoidal endothelial cells (HLSECs) and the adhesion of human neutrophils to HLSECs in vitro. Consistent with the protective role of CB2 receptor activation, CB2-/- mice develop increased I/R-induced tissue damage and proinflammatory phenotype. These findings suggest that oxidative/nitrosative stress and inflammatory stimuli may trigger endocannabinoid production, and indicate that targeting CB2 cannabinoid receptors may represent a novel protective strategy against I/R injury. We also demonstrate that CB2-/- mice have a normal hemodynamic profile.--Bátkai, S., Osei-Hyiaman, D., Pan, H., El-Assal, O., Rajesh, M., Mukhopadhyay, P., Hong, F., Harvey-White, J., Jafri, A., Haskó, G., Huffman, J. W., Gao, B., Kunos, G., Pacher, P. Cannabinoid-2 receptor mediates protection against hepatic ischemia/reperfusion injury.




This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
J. Gertsch, M. Leonti, S. Raduner, I. Racz, J.-Z. Chen, X.-Q. Xie, K.-H. Altmann, M. Karsak, and A. Zimmer
Beta-caryophyllene is a dietary cannabinoid
PNAS, July 1, 2008; 105(26): 9099 - 9104.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
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]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
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]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
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]

Home page
 J. Pharmacol. Exp. Ther.Home page
J. Munoz-Luque, J. Ros, G. Fernandez-Varo, S. Tugues, M. Morales-Ruiz, C. E. Alvarez, S. L. Friedman, V. Arroyo, and W. Jimenez
Regression of Fibrosis after Chronic Stimulation of Cannabinoid CB2 Receptor in Cirrhotic Rats
J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 475 - 483.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
A. Mallat and S. Lotersztajn
Endocannabinoids and Liver Disease. I. Endocannabinoids and their receptors in the liver
Am J Physiol Gastrointest Liver Physiol, January 1, 2008; 294(1): G9 - G12.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
M. Rajesh, H. Pan, P. Mukhopadhyay, S. Batkai, D. Osei-Hyiaman, G. Hasko, L. Liaudet, B. Gao, and P. Pacher
Pivotal Advance: Cannabinoid-2 receptor agonist HU-308 protects against hepatic ischemia/reperfusion injury by attenuating oxidative stress, inflammatory response, and apoptosis
J. Leukoc. Biol., December 1, 2007; 82(6): 1382 - 1389.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
H. F. Rosenberg
Endocannabinoids, cannabinoid receptors and inflammatory stress: an interview with Dr. Pal Pacher
J. Leukoc. Biol., December 1, 2007; 82(6): 1390 - 1392.
[Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
M. Rajesh, P. Mukhopadhyay, S. Batkai, G. Hasko, L. Liaudet, J. W. Huffman, A. Csiszar, Z. Ungvari, K. Mackie, S. Chatterjee, et al.
CB2-receptor stimulation attenuates TNF-{alpha}-induced human endothelial cell activation, transendothelial migration of monocytes, and monocyte-endothelial adhesion
Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2210 - H2218.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
S. Batkai, P. Mukhopadhyay, J. Harvey-White, R. Kechrid, P. Pacher, and G. Kunos
Endocannabinoids acting at CB1 receptors mediate the cardiac contractile dysfunction in vivo in cirrhotic rats
Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1689 - H1695.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
S. Batkai, M. Rajesh, P. Mukhopadhyay, G. Hasko, L. Liaudet, B. F. Cravatt, A. Csiszar, Z. Ungvari, and P. Pacher
Decreased age-related cardiac dysfunction, myocardial nitrative stress, inflammatory gene expression, and apoptosis in mice lacking fatty acid amide hydrolase
Am J Physiol Heart Circ Physiol, August 1, 2007; 293(2): H909 - H918.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Copyright © 2007 by The Federation of American Societies for Experimental Biology.