Activation of the liver X receptor protects against hepatic injury in endotoxemia by suppressing Kupffer cell activation

Shock
Yun Yong WangJ E Wang

Abstract

Recent reports have demonstrated that liver X receptors (LXRs) of the nuclear receptor family have anti-inflammatory effects on macrophages. Here we examine whether activation of LXR by the synthetic agonist GW3965 can ameliorate the liver injury/dysfunction caused by endotoxins in the rat. Male Wistar rats received GW3965 (0.3 mg/kg) or vehicle (50% dimethyl sulfoxide) 30 min before coadministration of lipopolysaccharide (LPS, 5 mg/kg i.v.) and peptidoglycan (1 mg/kg i.v.). Treatment with GW3965 attenuated the increase in the plasma levels of alanine aminotransferase and bilirubin (markers of liver injury/dysfunction) as well as the focal hepatocyte necrosis (histology) caused by coadministration of LPS and peptidoglycan. This protective effect of GW3965 treatment was associated with reduced infiltration of mast cells in the liver (histopathology) and reduced gene expression of the chemokines eotaxins 1 and 2, whereas MIP-2 mRNA levels were not affected. Plasma levels of tumor necrosis factor alpha and prostaglandin E2 were significantly attenuated by GW3965, whereas plasma interleukins 6 and 10 were not altered. High expression of LXRalpha mRNA was observed in Kupffer cell cultures, suggesting that Kupffer cells are targets o...Continue Reading

References

Nov 1, 1989·The Journal of Experimental Medicine·R D CurranR L Simmons
Jun 1, 1988·The Journal of Experimental Medicine·A Waage, T Espevik
Oct 24, 1995·Proceedings of the National Academy of Sciences of the United States of America·S J De KimpeJ R Vane
Feb 1, 1995·Shock·B G Harbrecht, T R Billiar
Jul 10, 1999·Science·H WangK J Tracey
Mar 10, 2001·The Journal of Clinical Investigation·S AlbertiJ A Gustafsson
Apr 18, 2001·International Archives of Allergy and Immunology·A de PaulisP Romagnani
Aug 16, 2001·American Journal of Physiology. Lung Cellular and Molecular Physiology·R C ReddyT J Standiford
Mar 20, 2002·The Journal of Biological Chemistry·Joyce J RepaDavid J Mangelsdorf
May 3, 2002·Journal of Medicinal Chemistry·Jon L CollinsTimothy M Willson
May 29, 2002·Proceedings of the National Academy of Sciences of the United States of America·Sean B JosephPeter Tontonoz
Dec 20, 2002·Nature·Carl Nathan
Jan 14, 2003·Nature Medicine·Sean B JosephPeter Tontonoz
Jan 18, 2003·The Journal of Biological Chemistry·Antonio CastrilloPeter Tontonoz
Feb 6, 2004·Critical Care Medicine·Jacob E WangChristoph Thiemermann
Sep 30, 2004·Nature Immunology·Kasper HoebeBruce Beutler
Nov 9, 2004·Atherosclerosis·Per-Arne SvenssonLena M S Carlsson

❮ Previous
Next ❯

Citations

Jun 15, 2012·Archivum Immunologiae Et Therapiae Experimentalis·Mónica Pascual-García, Annabel F Valledor
Jan 22, 2009·Pathology International·So TakegoshiMakoto Naito
Mar 12, 2010·World Journal of Gastroenterology : WJG·Zhong ZengYu-Jun Zhang
May 1, 2012·Trends in Pharmacological Sciences·Tomas JakobssonKnut R Steffensen
Feb 22, 2011·Gastroenterology·Michael Trauner, Emina Halilbasic
Apr 2, 2008·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·Z J LiuJ P Gong
Nov 28, 2008·Cardiovascular Therapeutics·Jerzy Bełtowski
Jan 20, 2012·Journal of Digestive Diseases·Yuan LiuXiong Ma
Aug 20, 2015·ACS Medicinal Chemistry Letters·Sayaka NomuraMinoru Ishikawa
Jul 26, 2011·Journal of Hepatology·Ariane Mallat, Sophie Lotersztajn
Sep 30, 2006·Biochimica Et Biophysica Acta·Petter Kirkeby RisøeMaria K Dahle
Aug 16, 2016·Cellular and Molecular Life Sciences : CMLS·Simon DucheixAntonio Moschetta
Jun 13, 2015·Experimental Biology and Medicine·Meng YangHaiping Wang
Mar 23, 2017·British Journal of Pharmacology·Fatima IqbalDemidmaa Tuvdendorj
Oct 17, 2008·Pharmacological Reviews·Nora Anderson, Jürgen Borlak
Nov 8, 2017·Seminars in Immunopathology·Antonella Carambia, Johannes Herkel
Nov 30, 2019·The Journal of Infectious Diseases·Fabrício O SoutoFernando Q Cunha
Nov 27, 2019·Cells·Ralf WeiskirchenMichael Huber
Mar 16, 2017·Pflügers Archiv : European journal of physiology·Zeinab Abdullah, Percy A Knolle
Aug 2, 2018·Journal of Mammary Gland Biology and Neoplasia·Xiaoyu HuYunhe Fu
Oct 17, 2019·International Journal of Molecular Sciences·Kaori Endo-Umeda, Makoto Makishima
Dec 12, 2020·Journal of Cellular Physiology·Lin ZhaoYang Yang
Nov 10, 2020·Hepatology Communications·Li GaoWen Xie
Feb 6, 2021·Cellular and Molecular Gastroenterology and Hepatology·Marica CarielloAntonio Moschetta

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bacterial Cell Wall Structure (ASM)

Bacterial cell walls are made of peptidoglycan (also called murein), which is made from polysaccharide chains cross-linked by unusual peptides containing D-amino acids. Here is the latest research on bacterial cell wall structures.

Bacterial Cell Wall Structure

Bacterial cell walls are made of peptidoglycan (also called murein), which is made from polysaccharide chains cross-linked by unusual peptides containing D-amino acids. Here is the latest research on bacterial cell wall structures.