Liver X receptor agonist treatment regulates inflammatory response after spinal cord trauma.
Liver X receptor alpha (LXRalpha) and LXRbeta are members of the nuclear receptor superfamily of ligand-activated transcription factors. The aim of this study was to investigate the effects of T0901317, a potent LXR receptor ligand, in a mouse model of spinal cord injury (SCI). SCI was induced by the application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy in mice. Treatment with T0901317, 1 and 6 h after the SCI, significantly decreased (i) the degree of spinal cord inflammation and tissue injury (histological score); (ii) neutrophil infiltration (myeloperoxidase activity); (iii) inducible nitric oxide synthase expression; (iv) nitrotyrosine, lipid peroxidation, and poly-ADP-ribose formation; (v) pro-inflammatory cytokines expression; (vi) nuclear factor-kappa B activation; and (vii) apoptosis (terminal deoxynucleotidyltransferase-mediated UTP end labeling staining, FAS ligand, Bax, and Bcl-2 expression). Moreover, T0901317 significantly ameliorated the loss of limb function (evaluated by motor recovery score). These data suggest that LXR ligand may be useful in the treatment of inflammation associated with SCI.
Paterniti
Irene
I
Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, 98100 Messina, Italy.
Genovese
Tiziana
T
Mazzon
Emanuela
E
Crisafulli
Concetta
C
Di Paola
Rosanna
R
Galuppo
Maria
M
Bramanti
Placido
P
Cuzzocrea
Salvatore
S
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D053222:Fas Ligand Protein / Q000378:metabolism; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology* / Q000627:therapeutic use; D020287:In Situ Nick-End Labeling / Q000379:methods; D007796:Laminectomy / Q000009:adverse effects; D015227:Lipid Peroxidation / Q000187:drug effects; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D009069:Movement Disorders / Q000188:drug therapy / Q000209:etiology; D009187:Myelitis / Q000188:drug therapy / Q000209:etiology; D016328:NF-kappa B / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000819:agonists* / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy / Q000209:etiology; D018709:Statistics, Nonparametric; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D053222:Fas Ligand Protein; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D016328:NF-kappa B; D052247:Nitric Oxide Synthase Type II; D057093:Orphan Nuclear Receptors; D009195:Peroxidase; D011064:Poly Adenosine Diphosphate Ribose; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D013449:Sulfonamides; D014443:Tyrosine; D051028:bcl-2-Associated X Protein; C000605214:Nr1h3 protein, mouse; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides; C024857:poly(ADP)-ribosylated proteins; C002744:3-nitrotyrosine