BioSpace Collaborative

Academic/Biomedical Research
News & Jobs
Biotechnology and Pharmaceutical Channel Medical Device and Diagnostics Channel Clinical Research Channel BioSpace Collaborative    Job Seekers:  Register | Login          Employers:  Register | Login  

NEWSLETTERS
Free Newsletters
Archive
My Subscriptions

NEWS
News by Subject
News by Disease
News by Date
PLoS
Search News
Post Your News
JoVE

CAREER NETWORK
Job Seeker Login
Most Recent Jobs
Search Jobs
Post Resume
Career Fairs
Career Resources
For Employers

HOTBEDS
Regional News
US & Canada
  Biotech Bay
  Biotech Beach
  Genetown
  Pharm Country
  BioCapital
  BioMidwest
  Bio NC
  BioForest
  Southern Pharm
  BioCanada East
  US Device
Europe
Asia

DIVERSITY

PROFILES
Company Profiles

INTELLIGENCE
Research Store

INDUSTRY EVENTS
Research Events
Post an Event
RESOURCES
Real Estate
Business Opportunities

PLoS By Category | Recent PLoS Articles
Critical Care and Emergency Medicine - Immunology - Surgery

STAT3 Regulates Monocyte TNF-Alpha Production in Systemic Inflammation Caused by Cardiac Surgery with Cardiopulmonary Bypass
Published: Tuesday, April 10, 2012
Author: Petrus R. de Jong et al.

by Petrus R. de Jong, Alvin W. L. Schadenberg, Theo van den Broek, Jeffrey M. Beekman, Femke van Wijk, Paul J. Coffer, Berent J. Prakken, Nicolaas J. G. Jansen

Background

Cardiopulmonary bypass (CPB) surgery initiates a controlled systemic inflammatory response characterized by a cytokine storm, monocytosis and transient monocyte activation. However, the responsiveness of monocytes to Toll-like receptor (TLR)-mediated activation decreases throughout the postoperative course. The purpose of this study was to identify the major signaling pathway involved in plasma-mediated inhibition of LPS-induced tumor necrosis factor (TNF)-a production by monocytes.

Methodology/Principal Findings

Pediatric patients that underwent CPB-assisted surgical correction of simple congenital heart defects were enrolled (n?=?38). Peripheral blood mononuclear cells (PBMC) and plasma samples were isolated at consecutive time points. Patient plasma samples were added back to monocytes obtained pre-operatively for ex vivo LPS stimulations and TNF-a and IL-6 production was measured by flow cytometry. LPS-induced p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-?B activation by patient plasma was assessed by Western blotting. A cell-permeable peptide inhibitor was used to block STAT3 signaling. We found that plasma samples obtained 4 h after surgery, regardless of pre-operative dexamethasone treatment, potently inhibited LPS-induced TNF-a but not IL-6 synthesis by monocytes. This was not associated with attenuation of p38 MAPK activation or I?B-a degradation. However, abrogation of the IL-10/STAT3 pathway restored LPS-induced TNF-a production in the presence of suppressive patient plasma.

Conclusions/Significance

Our findings suggest that STAT3 signaling plays a crucial role in the downregulation of TNF-a synthesis by human monocytes in the course of systemic inflammation in vivo. Thus, STAT3 might be a potential molecular target for pharmacological intervention in clinical syndromes characterized by systemic inflammation.

  More...

 

//-->