PURPOSE: To assess changes in peroxisome proliferator-activated receptor-gamma (PPARgamma) in peripheral blood mononuclear cells (PBMC) from critically ill children with sepsis. Additionally, to investigate the effects of sepsis on the endogenous activator of PPARgamma, 15-deoxy-(12,14)-PGJ(2) (15d-PGJ(2)), and the downstream targets of PPARgamma activity, adiponectin and resistin. METHODS: Single-center, prospective case-control study in critically ill children with systemic inflammatory response syndrome, sepsis or septic shock. RESULTS: PPARgamma nuclear protein expression was decreased but PPARgamma activity was increased in PBMC from children with septic shock compared with controls. PPARgamma activity on day 1 was significantly higher in patients with higher pediatric risk of mortality (PRISM) score compared with controls [mean 0.22 optical density (OD) +/- standard error of the mean (SEM) 0.03 versus 0.12 OD +/- 0.02; p < 0.001]. Patients with resolved sepsis had increased levels of the endogenous PPARgamma ligand, 15d-PGJ(2), compared with patients with systemic inflammatory response syndrome (SIRS) and septic shock (77.7 +/- 21.7 versus 58 +/- 16.5 pg/ml; p = 0.03). Plasma high-molecular-weight adiponectin (HMWA) and resistin levels were increased in patients with septic shock on day 1 and were significantly higher in patients with higher PRISM scores. Nonsurvivors from sepsis had higher resistin levels on the first day of hospitalization compared with survivors from septic shock [660 ng/ml, interquartile range (IQR) 585-833 ng/ml versus 143 ng/ml, IQR 66-342 ng/ml; p < 0.05]. CONCLUSIONS: Sepsis is associated with altered PPARgamma expression and activity in PBMC. Plasma adipokines correlate with risk of mortality scores in sepsis and may be useful biomarkers. Further studies are needed to understand the mechanisms underlying changes in PPARgamma in sepsis.
PURPOSE: To assess changes in peroxisome proliferator-activated receptor-gamma (PPARgamma) in peripheral blood mononuclear cells (PBMC) from critically ill children with sepsis. Additionally, to investigate the effects of sepsis on the endogenous activator of PPARgamma, 15-deoxy-(12,14)-PGJ(2) (15d-PGJ(2)), and the downstream targets of PPARgamma activity, adiponectin and resistin. METHODS: Single-center, prospective case-control study in critically ill children with systemic inflammatory response syndrome, sepsis or septic shock. RESULTS:PPARgamma nuclear protein expression was decreased but PPARgamma activity was increased in PBMC from children with septic shock compared with controls. PPARgamma activity on day 1 was significantly higher in patients with higher pediatric risk of mortality (PRISM) score compared with controls [mean 0.22 optical density (OD) +/- standard error of the mean (SEM) 0.03 versus 0.12 OD +/- 0.02; p < 0.001]. Patients with resolved sepsis had increased levels of the endogenous PPARgamma ligand, 15d-PGJ(2), compared with patients with systemic inflammatory response syndrome (SIRS) and septic shock (77.7 +/- 21.7 versus 58 +/- 16.5 pg/ml; p = 0.03). Plasma high-molecular-weight adiponectin (HMWA) and resistin levels were increased in patients with septic shock on day 1 and were significantly higher in patients with higher PRISM scores. Nonsurvivors from sepsis had higher resistin levels on the first day of hospitalization compared with survivors from septic shock [660 ng/ml, interquartile range (IQR) 585-833 ng/ml versus 143 ng/ml, IQR 66-342 ng/ml; p < 0.05]. CONCLUSIONS:Sepsis is associated with altered PPARgamma expression and activity in PBMC. Plasma adipokines correlate with risk of mortality scores in sepsis and may be useful biomarkers. Further studies are needed to understand the mechanisms underlying changes in PPARgamma in sepsis.
Authors: J M Way; C Z Görgün; Q Tong; K T Uysal; K K Brown; W W Harrington; W R Oliver; T M Willson; S A Kliewer; G S Hotamisligil Journal: J Biol Chem Date: 2001-05-23 Impact factor: 5.157
Authors: N Maeda; M Takahashi; T Funahashi; S Kihara; H Nishizawa; K Kishida; H Nagaretani; M Matsuda; R Komuro; N Ouchi; H Kuriyama; K Hotta; T Nakamura; I Shimomura; Y Matsuzawa Journal: Diabetes Date: 2001-09 Impact factor: 9.461
Authors: D S Straus; G Pascual; M Li; J S Welch; M Ricote; C H Hsiang; L L Sengchanthalangsy; G Ghosh; C K Glass Journal: Proc Natl Acad Sci U S A Date: 2000-04-25 Impact factor: 11.205
Authors: Terry P Combs; John A Wagner; Joel Berger; Tom Doebber; Wen-Jun Wang; Bei B Zhang; Michael Tanen; Anders H Berg; Stephen O'Rahilly; David B Savage; Krishna Chatterjee; Stuart Weiss; Patrick J Larson; Keith M Gottesdiener; Barry J Gertz; Maureen J Charron; Philipp E Scherer; David E Moller Journal: Endocrinology Date: 2002-03 Impact factor: 4.736
Authors: Jennifer M Kaplan; Paul W Hake; Alvin Denenberg; Marchele Nowell; Giovanna Piraino; Basilia Zingarelli Journal: Mol Med Date: 2010-08-19 Impact factor: 6.354
Authors: Jennifer M Kaplan; Basilia Zingarelli; Kelli Krallman; Sonya Tang Girdwood; Denise Lagory; Tomoyuki Mizuno; Lin Fei; Hector R Wong; Alexander A Vinks Journal: Intensive Care Med Date: 2018-09-25 Impact factor: 17.440
Authors: Adam D Irwin; Fiona Marriage; Limangeni A Mankhambo; Graham Jeffers; Ruwanthi Kolamunnage-Dona; Malcolm Guiver; Brigitte Denis; Elizabeth M Molyneux; Malcolm E Molyneux; Philip J Day; Enitan D Carrol Journal: BMC Med Genomics Date: 2012-05-04 Impact factor: 3.063
Authors: Massimo Antonelli; Elie Azoulay; Marc Bonten; Jean Chastre; Giuseppe Citerio; Giorgio Conti; Daniel De Backer; Herwig Gerlach; Goran Hedenstierna; Michael Joannidis; Duncan Macrae; Jordi Mancebo; Salvatore M Maggiore; Alexandre Mebazaa; Jean-Charles Preiser; Jerôme Pugin; Jan Wernerman; Haibo Zhang Journal: Intensive Care Med Date: 2011-02-03 Impact factor: 17.440