Anti-Inflammatory and Antiatherogenic Effects of the NLRP3 Inflammasome Inhibitor Arglabin in ApoE(2).Ki Mice Fed a High-Fat Diet - Biological Adaptation and Ageing Accéder directement au contenu
Article Dans Une Revue Circulation Année : 2015

Anti-Inflammatory and Antiatherogenic Effects of the NLRP3 Inflammasome Inhibitor Arglabin in ApoE(2).Ki Mice Fed a High-Fat Diet

Cecile Vindis
  • Fonction : Auteur
Muriel Laffargue
Veronique Mateo
  • Fonction : Auteur
Berthold Buechele
  • Fonction : Auteur
Monica Rubio Ayala
  • Fonction : Auteur
Menna El Gaafary
  • Fonction : Auteur
Tatiana Syrovets
  • Fonction : Auteur
Mohamed-Naceur Slimane
  • Fonction : Auteur
Tamas Fulop
Thomas Simmet
  • Fonction : Auteur
Khadija El Hadri
  • Fonction : Auteur
Amna Abderrazak
  • Fonction : Auteur
Dominique Couchie
  • Fonction : Auteur
Dler Faieeq Darweesh Mahmood
  • Fonction : Auteur
Rima Elhage

Résumé

Background-This study was designed to evaluate the effect of arglabin on the NLRP3 inflammasome inhibition and atherosclerotic lesion in ApoE 2 Ki mice fed a high-fat Western-type diet. Methods and Results-Arglabin was purified, and its chemical identity was confirmed by mass spectrometry. It inhibited, in a concentration-dependent manner, interleukin (IL)-1 beta and IL-18, but not IL-6 and IL-12, production in lipopolysaccharide and cholesterol crystal-activated cultured mouse peritoneal macrophages, with a maximum effect at approximate to 50 nmol/L and EC50 values for both cytokines of approximate to 10 nmol/L. Lipopolysaccharide and cholesterol crystals did not induce IL-1 beta and IL-18 production in Nlrp3(-/-) macrophages. In addition, arglabin activated autophagy as evidenced by the increase in LC3-II protein. Intraperitoneal injection of arglabin (2.5 ng/g body weight twice daily for 13 weeks) into female ApoE(2). Ki mice fed a high-fat diet resulted in a decreased IL-1 beta plasma level compared with vehicle-treated mice (5.2 +/- 1.0 versus 11.7 +/- 1.1 pg/mL). Surprisingly, arglabin also reduced plasma levels of total cholesterol and triglycerides to 41% and 42%, respectively. Moreover, arglabin oriented the proinflammatory M1 macrophages into the anti-inflammatory M2 phenotype in spleen and arterial lesions. Finally, arglabin treatment markedly reduced the median lesion areas in the sinus and whole aorta to 54% (P=0.02) and 41% (P=0.02), respectively. Conclusions-Arglabin reduces inflammation and plasma lipids, increases autophagy, and orients tissue macrophages into an anti-inflammatory phenotype in ApoE 2. Ki mice fed a high-fat diet. Consequently, a marked reduction in atherosclerotic lesions was observed. Thus, arglabin may represent a promising new drug to treat inflammation and atherosclerosis.

Dates et versions

hal-01543968 , version 1 (21-06-2017)

Identifiants

Citer

Cecile Vindis, Muriel Laffargue, Veronique Mateo, Berthold Buechele, Monica Rubio Ayala, et al.. Anti-Inflammatory and Antiatherogenic Effects of the NLRP3 Inflammasome Inhibitor Arglabin in ApoE(2).Ki Mice Fed a High-Fat Diet. Circulation, 2015, 131 (12), pp.1061-1070. ⟨10.1161/CIRCULATIONAHA.114.013730⟩. ⟨hal-01543968⟩
179 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More