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

Concetta Crisafulli, Emanuela Mazzon, Irene Paterniti, Maria Galuppo, Placido Bramanti, Salvatore Cuzzocrea

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Liver × receptor α (LXRα) and β (LXRβ) 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-α, (TNF-α) and interleukin-1β (IL-1β). 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.

Original languageEnglish
Article number19
JournalRespiratory Research
Volume11
DOIs
Publication statusPublished - Feb 22 2010

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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