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Inducing Acute Lung Injury in Mice by Direct Intratracheal Lipopolysaccharide Instillation
Published on: July 6, 2019
GW0742, a high-affinity PPAR -beta/delta agonist, inhibits acute lung injury in mice
Rosanna Di Paola1, Concetta Crisafulli, Emanuela Mazzon
1IRCCS Centro Neurolesi Bonino-Pulejo, University of Messina, Italy.
Abstract:
Several lines of evidence suggest a biological role for peroxisome proliferator-activated receptor (PPAR) beta/delta in the pathogenesis of a number of diseases. The aim of this study was to investigate the effects of a high-affinity PPAR-beta/delta agonist, GW0742, in a mouse model of carrageenan (CAR)-induced pleurisy. Injection of CAR into the pleural cavity of mice elicited an acute inflammatory response characterized by accumulation of fluid containing a large number of neutrophils (polymorphonuclear leukocytes) in the pleural cavity, infiltration of polymorphonuclear leukocytes in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate, TNF-alpha, and IL-1beta. Furthermore, CAR induced lung apoptosis (Bax and Bcl-2 expression), and nitrotyrosine formation was determined by immunohistochemical analysis of lung tissues. Administration of GW0742 (0.3 mg/kg, i.p. bolus) 30 min before and 30 min after a challenge with CAR caused a reduction in all the parameters of inflammation measured. Thus, based on these findings, we propose that a PPAR-beta/delta agonist such as GW0742 may be useful in the treatment of various inflammatory diseases.
Insights
Peroxisome proliferator-activated receptor (PPAR) beta/delta activation with GW0742 significantly reduced inflammation in a mouse model of carrageenan-induced pleurisy. This suggests PPAR beta/delta agonists may treat inflammatory diseases.
Area of Science:
- Pharmacology
- Immunology
- Molecular Biology
Background:
- Peroxisome proliferator-activated receptor (PPAR) beta/delta is implicated in disease pathogenesis.
- Understanding its role in inflammation is crucial for therapeutic development.
Purpose of the Study:
- To investigate the anti-inflammatory effects of the PPAR beta/delta agonist GW0742.
- To evaluate GW0742 in a carrageenan (CAR)-induced pleurisy mouse model.
Main Methods:
- Carrageenan injection induced acute inflammation in mice.
- GW0742 was administered intraperitoneally before and after carrageenan challenge.
- Inflammatory markers including neutrophils, lipid peroxidation, nitrite/nitrate, TNF-alpha, IL-1beta, apoptosis, and nitrotyrosine were assessed.
Main Results:
- Carrageenan challenge led to significant pleurisy, neutrophil infiltration, oxidative stress, and pro-inflammatory cytokine production.
- GW0742 administration markedly reduced all measured parameters of inflammation.
- Apoptosis and nitrotyrosine formation in lung tissue were also attenuated by GW0742.
Conclusions:
- PPAR beta/delta activation by GW0742 effectively suppresses carrageenan-induced pleurisy in mice.
- GW0742 demonstrates potential as a therapeutic agent for inflammatory conditions.
- Targeting PPAR beta/delta may offer a novel strategy for treating inflammatory diseases.
