Effects of Liver x receptor agonist treatment on signal transduction pathways in acute lung inflammation.
BACKGROUND
Liver x receptor alpha (LXRalpha) and beta (LXRbeta) are members of the nuclear receptor super family of ligand-activated transcription factors, a super family which includes the perhaps better known glucocorticoid receptor, estrogen receptor, thyroid receptor, and peroxisome proliferator-activated receptors. There is limited evidence that LXL activation may reduces acute lung inflammation. The aim of this study was to investigate the effects of T0901317, a potent LXR receptor ligand, in a mouse model of carrageenan-induced pleurisy.


METHODS
Injection of carrageenan into the pleural cavity of mice elicited an acute inflammatory response characterized by: accumulation of fluid containing a large number of neutrophils (PMNs) in the pleural cavity, infiltration of PMNs in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate (NOx), tumor necrosis factor-alpha, (TNF-alpha) and interleukin-1beta (IL-1beta). Furthermore, carrageenan induced the expression of iNOS, nitrotyrosine and PARP, as well as induced apoptosis (TUNEL staining and Bax and Bcl-2 expression) in the lung tissues.


RESULTS
Administration of T0901317, 30 min after the challenge with carrageenan, caused a significant reduction in a dose dependent manner of all the parameters of inflammation measured.


CONCLUSIONS
Thus, based on these findings we propose that LXR ligand such as T0901317, may be useful in the treatment of various inflammatory diseases.
Crisafulli
Concetta
C
Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Italy.
Mazzon
Emanuela
E
Paterniti
Irene
I
Galuppo
Maria
M
Bramanti
Placido
P
Cuzzocrea
Salvatore
S
D055371:Acute Lung Injury; D000818:Animals; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage*; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D057093:Orphan Nuclear Receptors / Q000819:agonists*; D010998:Pleurisy / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D011014:Pneumonia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013449:Sulfonamides / Q000008:administration & dosage*; D016896:Treatment Outcome; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D013449:Sulfonamides; C000605214:Nr1h3 protein, mouse; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides