Liver X receptor agonist treatment reduced splanchnic ischemia and reperfusion injury

Journal of Leukocyte Biology

Emanuela Mazzon³  Tiziana Genovese¹  Placido Bramanti³  Salvatore Cuzzocrea¹  Irene Paterniti²  Concetta Crisafulli²  Maria Galuppo²  Alessandro Cappellani⁴  Rosanna Di Paola³ 

[1] Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Messina, Italy; IRCCS Centro Neurolesi “Bonino-Pulejo,” Messina, Italy; and Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Messina, Italy; Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Messina, Italy; IRCCS Centro Neurolesi “Bonino-Pulejo,” Messina, Italy; and IRCCS Centro Neurolesi “Bonino-Pulejo,” Messina, Italy; and Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Messina, Italy; IRCCS Centro Neurolesi “Bonino-Pulejo,” Messina, Italy; andDepartment of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Messina, Italy; Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Messina, Italy; Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Messina, Italy;;IRCCS Centro Neurolesi “Bonino-Pulejo,” Messina, Italy; and IRCCS Centro Neurolesi “Bonino-Pulejo,” Messina, Italy; and IRCCS Centro Neurolesi “Bonino-Pulejo,” Messina, Italy; and;Department of Surgery, University of Catania, Catania, Italy Department of Surgery, University of Catania, Catania, Italy Department of Surgery, University of Catania, Catania, Italy

关键词: artery occlusion;    oxygen-free radicals;    apoptosis;    adhesion molecules;   

DOI  :  10.1189/jlb.0609438

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

LXR is another member of the superfamily of nuclear hormone receptors that heterodimerizes with RXR and regulates the intracellular levels of cholesterol through gene induction of enzymes and proteins involved in the cholesterol metabolism and transport. LXR ligands inhibit the gene expression of proinflammatory mediators in immunostimulated macrophages; in vivo studies have shown that activation of LXR reduces the inflammatory response in a murine model of contact dermatitis and atherosclerosis. No reports have addressed a role for LXRs in pathophysiology of intestinal ischemia. The aim of this study was to investigate the effects of T0901317, a potent LXR ligand, in a mouse model of SAO shock, which was induced by clamping the superior mesenteric artery and the celiac trunk, resulting in a total occlusion of these arteries for 30 min. After this period of occlusion, the clamps were removed. Mice were killed at 60 min after reperfusion. This study provides the evidence that T0901317, LXR agonist, modulates: the development of SAO shock; the infiltration of the tissue with PMNs; the expression of TNF-α and IL-1β; the nitration of tyrosine residues; NF-κB expression; the MAPK phosphorylation (ERK, JNK, and p38); FasL; apoptosis; Bax and Bcl-2 expression; and the degree of tissue injury caused by SAO shock. Our results imply that LXR agonists may be useful in the therapy of inflammation.

【 授权许可】

Unknown