Shenkar R, Schwartz M D, Terada L S, Repine J E, McCord J, Abraham E
Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, USA.
Am J Physiol. 1996 May;270(5 Pt 1):L729-35. doi: 10.1152/ajplung.1996.270.5.L729.
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.
出血会迅速增加肺部促炎和免疫调节细胞因子的表达。多种细胞因子基因的启动子区域存在核转录调节因子（NF）-κB和NF-IL6（C/EBPβ）的结合元件，包括那些在失血后表达增加的基因。在本实验中，我们发现，出血1小时后从小鼠获取的肺单核细胞中NF-κB在体内的激活增加，但脾细胞中未增加。相反，出血并未激活肺细胞或脾细胞中的NF-IL6。预先喂食富含钨的饮食抑制黄嘌呤氧化酶可防止出血诱导的肺细胞中NF-κB的激活。在体外将脾细胞与黄嘌呤氧化酶一起孵育可激活NF-κB，但不能激活NF-IL6。锰超氧化物歧化酶可抑制黄嘌呤氧化酶诱导的NF-κB激活，但过氧化氢酶不能。这些结果表明，黄嘌呤氧化酶介导的超氧化物阴离子依赖性NF-κB激活在体内和体外均会发生。该机制可能有助于出血后肺部细胞因子反应的增加。
