Hemorrhage activates NF-kappa B in murine lung mononuclear cells in vivo

被引:71
作者
Shenkar, R
Schwartz, MD
Terada, LS
Repine, JE
McCord, J
Abraham, E
机构
[1] UNIV COLORADO, HLTH SCI CTR, DIV PULM SCI & CRIT CARE MED, DENVER, CO 80262 USA
[2] WEBB WARING INST BIOMED RES, DENVER, CO 80262 USA
关键词
transcription factors; promoter; gene regulation; cytokines; oxygen radicals;
D O I
10.1152/ajplung.1996.270.5.L729
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Hemorrhage rapidly increases the expression of proinflammatory and immunoregulatory cytokines in the lungs. Binding elements for the nuclear transcriptional regulatory factors (NF)-kappa B and NF-IL6 (C/EBP beta) are present in the promoter regions of multiple cytokine genes, including those whose expression is increased after blood loss. In the present experiments, we found increased activation in vivo of NF-kappa B in lung mononuclear cells, but not in splenocytes, taken from mice 1 h after hemorrhage. In contrast, hemorrhage did not activate NF-IL6 in lung cells or splenocytes. Inhibition of xanthine oxidase by prior feeding of a tungsten-enriched diet prevented hemorrhage-induced activation in lung cells of NF-kappa B. Incubating splenocytes in vitro with xanthine oxidase activated NF-kappa B but not NF-IL6. Xanthine oxidase-induced activation of NF-kappa B was inhibited by manganese superoxide dismutase, but not by catalase. These results suggest that xanthine oxidase-mediated superoxide anion-dependent activation of NF-kappa B occurs in vivo and in vitro. This mechanism may contribute to increased lung cytokine responses after hemorrhage.
引用
收藏
页码:L729 / L735
页数:7
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