Protective role of peroxisome proliferator-activated receptor-β/δ in septic shock.

Détails

ID Serval
serval:BIB_0E71863AACE2
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Protective role of peroxisome proliferator-activated receptor-β/δ in septic shock.
Périodique
American Journal of Respiratory and Critical Care Medicine
Auteur(s)
Kapoor A., Shintani Y., Collino M., Osuchowski M.F., Busch D., Patel N.S., Sepodes B., Castiglia S., Fantozzi R., Bishop-Bailey D., Mota-Filipe H., Yaqoob M.M., Suzuki K., Bahrami S., Desvergne B., Mitchell J.A., Thiemermann C.
ISSN
1535-4970[electronic], 1073-449X[linking]
Statut éditorial
Publié
Date de publication
2010
Volume
182
Numéro
12
Pages
1506-1515
Langue
anglais
Résumé
Rationale: Peroxisome proliferator activated receptor (PPAR)-beta/delta is a transcription factor that belongs to the PPAR nuclear hormone receptor family, but the role of PPAR-beta/delta in sepsis is unknown.
Objectives: We investigated the role of PPAR-beta/delta in murine models of LPS-induced organ injury and dysfunction and cecal ligation and puncture (CLP)-induced polymicrobial sepsis.
Methods: Wild-type (WT) and PPAR-beta/delta knockout (1(0) mice and C57BL/6 mice were subjected to LPS for 16 hours. C57BL/6 mice received the PPAR-beta/delta agonist GW0742 (0.03 mg/kg intravenously, 1 h after LPS) or GW0742 plus the PPAR-beta/delta antagonist GSK0660 (0.1 mg/kg intravenously, 30 min before LPS). CD-1 mice subjected to CLP received GW0742 or GW0742 plus GSK0660.
Measurements and Main Results: In PPAR-beta/delta KO mice, endotoxemia exacerbated organ injury and dysfunction (cardiac, renal, and hepatic) and inflammation (lung) compared with WT mice. In C57BL/6 mice subjected to endotoxemia, GW0742 significantly (1) attenuated organ (cardiac and renal) dysfunction and inflammation (lung); (2) increased the phosphorylation of Akt and glycogen synthase kinase (GSK)-3 beta; (3) attenuated the increase in extracellular signal-regulated kinase (ERK)1/2 and signal transducer and activator of transcription (STAT)-3 phosphorylation; and (4) attenuated the activation of nuclear factor (NF)-kappa B and the expression of inducible nitric oxide synthase (iNOS). In CD-1 mice subjected to CLP, GW0742 improved 10-day survival. All the observed beneficial effects of GW0742 were attenuated by the PPAR-beta/delta antagonist GSK0660.
Conclusions: PPAR-beta/delta protects against multiple organ injury and dysfunction, and inflammation caused by endotoxic shock and improves survival in polymicrobial sepsis by a mechanism that may involve activation of Akt and inhibition of GSK-3 beta and NF-kappa B.
Mots-clé
Animals, Disease Models, Animal, Glycogen Synthase Kinase 3/metabolism, Male, Mice, Mice, Inbred C57BL, NF-kappa B/metabolism, Nitric Oxide Synthase Type II/biosynthesis, PPAR delta/metabolism, PPAR-beta/metabolism, Phosphorylation/drug effects, Proto-Oncogene Proteins c-akt/metabolism, Shock, Septic/metabolism, Shock, Septic/prevention & control, Signal Transduction, Sulfones/pharmacology, Thiazoles/pharmacology, Thiophenes/pharmacology
Pubmed
Web of science
Création de la notice
08/03/2011 18:43
Dernière modification de la notice
20/08/2019 13:35
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