Protective role of cannabinoid receptor 2 activation in galactosamine/lipopolysaccharide-induced acute liver failure through regulation of macrophage polarization and microRNAs

The Journal of Pharmacology and Experimental Therapeutics
Sunil TomarPrakash Nagarkatti

Abstract

Acute liver failure (ALF) is a potentially life-threatening disorder without any effective treatment strategies. d-Galactosamine (GalN)/lipopolysaccharide (LPS)-induced ALF is a widely used animal model to identify novel hepato-protective agents. In the present study, we investigated the potential of a cannabinoid receptor 2 (CB2) agonist, JWH-133 [(6aR,10aR)-3-(1,1-dimethylbutyl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran], in the amelioration of GalN/LPS-induced ALF. JWH-133 treatment protected the mice from ALF-associated mortality, mitigated alanine transaminase and proinflammatory cytokines, suppressed histopathological and apoptotic liver damage, and reduced liver infiltration of mononuclear cells (MNCs). Furthermore, JWH-133 pretreatment of M1/M2-polarized macrophages significantly increased the secretion of anti-inflammatory cytokine interleukin-10 (IL-10) in M1 macrophages and potentiated the expression of M2 markers in M2-polarized macrophages. In vivo, JWH-133 treatment also suppressed ALF-triggered expression of M1 markers in liver MNCs, while increasing the expression of M2 markers such as Arg1 and IL-10. microRNA (miR) microarray analysis revealed that JWH-133 treatment altered the expression of o...Continue Reading

References

Apr 12, 1997·Lancet·A Mas, J Rodés
Apr 13, 2000·International Journal of Experimental Pathology·T M Rahman, H J Hodgson
May 9, 2000·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·M NowakL L Moldawer
Feb 22, 2001·The Journal of Clinical Investigation·G SassG Tiegs
Aug 2, 2002·Cell·Koichi KobayashiRichard A Flavell
Jul 9, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Takayuki MasakiHironobu Yoshimatsu
Feb 4, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·James Neuberger
Mar 15, 2005·Gastroenterology·Boris JulienSophie Lotersztajn
May 23, 2006·Nature Medicine·Fatima Teixeira-ClercSophie Lotersztajn
Sep 14, 2006·Pharmacological Reviews·Pál PacherGeorge Kunos
Mar 1, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sándor BátkaiPál Pacher
Oct 24, 2007·British Journal of Pharmacology·S LotersztajnA Mallat
Nov 3, 2007·American Journal of Physiology. Gastrointestinal and Liver Physiology·A Mallat, S Lotersztajn
Nov 6, 2007·British Journal of Pharmacology·A M Miller, N Stella
Nov 22, 2007·The Journal of Pharmacology and Experimental Therapeutics·Javier Muñoz-LuqueWladimiro Jiménez
Feb 23, 2008·American Journal of Physiology. Gastrointestinal and Liver Physiology·George Kunos, Douglas Osei-Hyiaman
Feb 29, 2008·Cytokine·Yong-Chen LuPamela S Ohashi
Sep 20, 2008·Journal of Hepatology·Charalambos Gustav AntoniadesDiego Vergani
Jul 4, 2009·World Journal of Gastroenterology : WJG·María-Jesús TuñónJavier González-Gallego
Sep 5, 2009·Journal of Gastroenterology·Annarosa FloreaniNora V Bergasa
Jan 26, 2010·Nature Reviews. Immunology·Ryan M O'ConnellDavid Baltimore
Jul 3, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Fatima Teixeira-ClercSophie Lotersztajn
Jul 20, 2010·Lancet·William BernalJulia Wendon
Oct 5, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·James P Nolan
Jan 22, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Joseph TamGeorge Kunos
Feb 19, 2011·Nature Reviews. Immunology·Luke A O'NeillClaire E McCoy
May 25, 2011·Journal of Biomedical Informatics·Harsh DweepNorbert Gretz
Jul 8, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Alexandre LouvetSophie Lotersztajn
Mar 2, 2012·The Journal of Clinical Investigation·Antonio Sica, Alberto Mantovani
Mar 27, 2012·Seminars in Respiratory and Critical Care Medicine·William M Lee

❮ Previous
Next ❯

Citations

Feb 16, 2016·International Journal of Molecular Sciences·Irmgard Tegeder
Apr 30, 2016·Toxicology and Applied Pharmacology·Irene M WohlmanJeffrey D Laskin
Sep 7, 2016·Mediators of Inflammation·Kathleen L McCoy
Dec 4, 2019·Journal of Clinical Gastroenterology·Ece UnalJohn H Marks
Jun 20, 2017·Pharmacological Reports : PR·Efrat Finkin-GronerMarta Weinstock
Jul 9, 2017·Proceedings of the National Academy of Sciences of the United States of America·Daniel R McDougleAditi Das
Apr 8, 2020·Evidence-based Complementary and Alternative Medicine : ECAM·Bin XuLi Xu
Dec 8, 2020·Journal of Developmental Origins of Health and Disease·Oyekoya T AyonrindeOyekunle K Ayonrinde
Jan 7, 2020·Seminars in Cancer Biology·Naiem T IssaSivanesan Dakshanamurthy
Jun 10, 2021·International Immunopharmacology·Hirva K BhattP S S Rao
May 12, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Chongyang QiuXimo Wang

❮ Previous
Next ❯

Related Concepts

Related Feeds