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Trauma-hemorrhage inhibits splenic dendritic cell proinflammatory cytokine production via a mitogen-activated protein kinase process.
- Source :
-
American Journal of Physiology: Cell Physiology . Mar2008, Vol. 294 Issue 3, pC754-C764. 11p. 7 Graphs. - Publication Year :
- 2008
-
Abstract
- Although splenic dendritic cell (DC) functions are markedly altered following trauma-hemorrhage, the mechanism(s) responsible for the altered DC functions remains unknown. We hypothesized that trauma-hemorrhage inhibits DC function via suppressing toll-like receptor 4 (TLR4) expression and mitogen-activated protein kinases (MAPKs). To examine this, male C3H/HeN (6-8 wk) mice were randomly assigned to sham operation or trauma-hemorrhage. Trauma-hemorrhage was induced by midline laparotomy and ~90 mm of hypotension [blood pressure (BP) 35 mmHg], followed by fluid resuscitation (4× the shed blood volume in the form of Ringer lactate). Two hours later, mice were euthanized, splenic DCs were isolated, and the changes in their MAPK activation, TLR4-MD-2 expression, and ability to produce cytokines were measured. The results indicate that trauma-hemorrhage downregulated the lipopolysaccharide (LPS)-induced MAPK activation in splenic DCs. In addition to the decrease in MAPK activation, surface expression of TLR4-MD-2 was suppressed following trauma-hemorrhage. Furthermore, LPS-induced cytokine production from splenic DCs was also suppressed following trauma-hemorrhage. These findings thus suggest that the decrease in TLR4-MD-2 and MAPK activation may contribute to the LPS hyporesponsiveness of splenic DCs following trauma-hemorrhage. Hyporesponsiveness of splenic DCs was also found after stimulation with the TLR2 agonist zymosan. Our results may thus explain the profound immunosuppression that is known to occur under those conditions. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03636143
- Volume :
- 294
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- American Journal of Physiology: Cell Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 31445710
- Full Text :
- https://doi.org/10.1152/ajpcell.00494.2007