S Fortis1, R G Khadaroo, J J Haitsma, H Zhang. 1. Keenan Research Center for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada; Department of Anaesthesia, University of Toronto, Toronto, ON, Canada; Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada; Department of Physiology, University of Toronto, Toronto, ON, Canada.
Abstract
BACKGROUND: Osteopontin (OPN) is a multifunctional glycoprotein with pro-inflammatory properties. In severe sepsis, levels of plasma OPN are significantly higher in non-survivors than in survivors. We hypothesized that OPN results in greater inflammation and worse outcome through modulation of endogenous glucocorticoid production in sepsis. METHODS AND RESULTS: Sepsis was induced by cecal ligation and puncture (CLP) in wild type (WT) and OPN gene knockout (OPN(-/-) ) mice. In response to sepsis, the OPN(-/-) mice had lower levels of plasma cytokines and chemokines than the WT mice. The levels of corticosterone in plasma were similar between WT and OPN(-/-) sham animals but they increased 24 h after CLP induction in the WT mice, but not in the OPN(-/-) mice. The mortality rate was lower in the OPN(-/-) mice than in the WT mice. CONCLUSION: OPN is associated with greater inflammatory response and increased mortality, despite the higher corticosterone levels in plasma. Corticosterone production is not impaired in the absence of OPN.
BACKGROUND:Osteopontin (OPN) is a multifunctional glycoprotein with pro-inflammatory properties. In severe sepsis, levels of plasma OPN are significantly higher in non-survivors than in survivors. We hypothesized that OPN results in greater inflammation and worse outcome through modulation of endogenous glucocorticoid production in sepsis. METHODS AND RESULTS:Sepsis was induced by cecal ligation and puncture (CLP) in wild type (WT) and OPN gene knockout (OPN(-/-) ) mice. In response to sepsis, the OPN(-/-) mice had lower levels of plasma cytokines and chemokines than the WT mice. The levels of corticosterone in plasma were similar between WT and OPN(-/-) sham animals but they increased 24 h after CLP induction in the WT mice, but not in the OPN(-/-) mice. The mortality rate was lower in the OPN(-/-) mice than in the WT mice. CONCLUSION:OPN is associated with greater inflammatory response and increased mortality, despite the higher corticosterone levels in plasma. Corticosterone production is not impaired in the absence of OPN.
Authors: S Ashkar; G F Weber; V Panoutsakopoulou; M E Sanchirico; M Jansson; S Zawaideh; S R Rittling; D T Denhardt; M J Glimcher; H Cantor Journal: Science Date: 2000-02-04 Impact factor: 47.728
Authors: Gerritje J W van der Windt; Arie J Hoogendijk; Marcel Schouten; Tijmen J Hommes; Alex F de Vos; Sandrine Florquin; Tom van der Poll Journal: J Infect Dis Date: 2011-06-15 Impact factor: 5.226
Authors: Z Krozowski; K X Li; K Koyama; R E Smith; V R Obeyesekere; A Stein-Oakley; H Sasano; C Coulter; T Cole; K E Sheppard Journal: J Steroid Biochem Mol Biol Date: 1999 Apr-Jun Impact factor: 4.292
Authors: Shirley H J Mei; Jack J Haitsma; Claudia C Dos Santos; Yupu Deng; Patrick F H Lai; Arthur S Slutsky; W Conrad Liles; Duncan J Stewart Journal: Am J Respir Crit Care Med Date: 2010-06-17 Impact factor: 21.405
Authors: Gerritje J W van der Windt; W Joost Wiersinga; Catharina W Wieland; Ivo C S I Tjia; Nicholas P Day; Sharon J Peacock; Sandrine Florquin; Tom van der Poll Journal: PLoS Negl Trop Dis Date: 2010-08-31
Authors: Rosanna Vaschetto; Stefania Nicola; Carlo Olivieri; Elena Boggio; Fabio Piccolella; Riccardo Mesturini; Federica Damnotti; Davide Colombo; Paolo Navalesi; Francesco Della Corte; Umberto Dianzani; Annalisa Chiocchetti Journal: Intensive Care Med Date: 2008-09-20 Impact factor: 17.440
Authors: Christoph Roderburg; Fabian Benz; David Vargas Cardenas; Matthias Lutz; Hans-Joerg Hippe; Tom Luedde; Christian Trautwein; Norbert Frey; Alexander Koch; Frank Tacke; Mark Luedde Journal: Crit Care Date: 2015-06-26 Impact factor: 9.097
Authors: Luigi Mario Castello; Marco Baldrighi; Luca Molinari; Livia Salmi; Vincenzo Cantaluppi; Rosanna Vaschetto; Greta Zunino; Marco Quaglia; Mattia Bellan; Francesco Gavelli; Paolo Navalesi; Gian Carlo Avanzi; Annalisa Chiocchetti Journal: Cells Date: 2019-02-18 Impact factor: 6.600