Effects of Liver x receptor agonist treatment on signal transduction pathways in acute lung inflammation.

Abstract

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.

• Authors: Concetta Crisafulli, Emanuela Mazzon, Irene Paterniti, Maria Galuppo, Placido Bramanti, Salvatore Cuzzocrea
• Journal: Respiratory research (Respir Res) Vol. 11 Pg. 19 (Feb 22 2010) ISSN: 1465-993X [Electronic] England
• PMID: 20175894 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hydrocarbons, Fluorinated
• Liver X Receptors
• Nr1h3 protein, mouse
• Orphan Nuclear Receptors
• Sulfonamides
• T0901317

Topics

• Acute Lung Injury
• Animals
• Hydrocarbons, Fluorinated (administration & dosage)
• Liver X Receptors
• Male
• Mice
• Orphan Nuclear Receptors (agonists)
• Pleurisy (complications, drug therapy, metabolism)
• Pneumonia (complications, drug therapy, metabolism)
• Signal Transduction (drug effects)
• Sulfonamides (administration & dosage)
• Treatment Outcome