Induction of early inflammatory gene expression in a murine model of nonresuscitated, fixed-volume hemorrhage.
The etiology of many end-organ problems associated with hemorrhage has been attributed to the inflammatory response to hemorrhage. In a murine model of nonresuscitated, fixed-volume hemorrhage, we sought to elucidate the role that hemorrhagic insult alone plays in the generation of the early inflammatory cascade. Differences could be appreciated as early as 1 h post-hemorrhage, with consistent differences detected by 3 h in all of the major cytokine genes studied. Significant upregulation of IL-1beta , IL-6, TNF-alpha, and IL-10 mRNA expression was observed in both the liver and lung samples of mice subjected to fixed-volume hemorrhage when compared with sham-hemorrhaged mice. The cyclooxygenase-2 (COX-2) and inducible nitric oxide synthetase (iNOS) genes also were upregulated in the livers and lungs of hemorrhaged mice. Finally, expression of the genes that encode the Toll-like receptors (TLR)-2 and -4 was increased by hemorrhage. Taken collectively, these data demonstrate that the initial inflammatory cascade associated with hemorrhage occurs within hours after the initial hemorrhagic event, and can be associated with significant modulation of expression of key pro- and anti-inflammatory cytokine, enzyme, and TLR genes, suggesting that these may be possible new therapeutic targets.
Rajnik
Michael
M
Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799, USA.
Salkowski
Cindy A
CA
Thomas
Karen E
KE
Li
Ying-Yue
YY
Rollwagen
Florence M
FM
Vogel
Stefanie N
SN
D000818:Animals; D001483:Base Sequence; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004195:Disease Models, Animal; D029721:Drosophila Proteins; D005260:Female; D015870:Gene Expression; D006470:Hemorrhage / Q000150:complications* / Q000235:genetics*; D007249:Inflammation / Q000209:etiology* / Q000235:genetics*; D007527:Isoenzymes / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics; D013997:Time Factors; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors
D016207:Cytokines; D018076:DNA, Complementary; D029721:Drosophila Proteins; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases