Trauma-hemorrhage inhibits splenic dendritic cell proinflammatory cytokine production via a mitogen-activated protein kinase process

Takashi Kawasaki, Mashkoor A. Choudhry, Martin G. Schwacha, Satoshi Fujimi, James A. Lederer, Kirby I. Bland, Irshad H. Chaudry

Research output: Contribution to journalArticle

12 Scopus citations

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 min of hypotension [blood pressure (BP) 35 mmHg], followed by fluid resuscitation (4x 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.

Original languageEnglish (US)
Pages (from-to)C754-C764
JournalAmerican Journal of Physiology - Cell Physiology
Volume294
Issue number3
DOIs
StatePublished - Mar 2008
Externally publishedYes

Keywords

  • Lipopolysaccharide
  • Splenic dendritic cell
  • Toll-like receptor 4 expression
  • Toll-like receptors

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Fingerprint Dive into the research topics of 'Trauma-hemorrhage inhibits splenic dendritic cell proinflammatory cytokine production via a mitogen-activated protein kinase process'. Together they form a unique fingerprint.

Cite this