title: Liver X receptor agonist treatment reduced splanchnic ischemia and reperfusion injury.
abstract: 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-alpha and IL-1beta; the nitration of tyrosine residues; NF-kappaB 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.
authors.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, 98100 Messina, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Crisafulli
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
authors.forename: Irene
authors.initials: I
authors.lastname: Paterniti
authors.forename: Maria
authors.initials: M
authors.lastname: Galuppo
authors.forename: Tiziana
authors.initials: T
authors.lastname: Genovese
authors.forename: Placido
authors.initials: P
authors.lastname: Bramanti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cappellani
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000276:immunology / Q000378:metabolism; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000276:immunology; D007421:Intestine, Small / Q000098:blood supply* / Q000276:immunology / Q000378:metabolism; D000071518:Liver X Receptors; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000096:biosynthesis / Q000276:immunology; D057093:Orphan Nuclear Receptors / Q000819:agonists* / Q000276:immunology / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D047488:Retinoid X Receptors / Q000276:immunology / Q000378:metabolism; D013152:Splanchnic Circulation / Q000187:drug effects / Q000276:immunology; D013449:Sulfonamides / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000276:immunology; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D002784:Cholesterol; D006845:Hydrocarbons, Fluorinated; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D000071518:Liver X Receptors; D016328:NF-kappa B; D057093:Orphan Nuclear Receptors; D047488:Retinoid X Receptors; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; C494827:Bax protein, mouse; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides