Early activation of pulmonary nuclear factor κB and nuclear factor interleukin-6 in polymicrobial sepsis
Early activation of pulmonary nuclear factor κB and nuclear factor interleukin-6 in polymicrobial sepsis
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DOI：
10.1097/00005373-199904000-00006
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发表时间：
1999-04-01
影响因子：
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通讯作者：
Williams, DL
中科院分区：
文献类型：
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作者：
Browder, W;Ha, TZ;Williams, DL
背景：转录因子的激活可能是脓毒症综合征和成人呼吸窘迫综合征的病理生理过程中的关键步骤。本研究探讨了肺核因子κ B的活化（NF κ B）和核因子白细胞介素-6（NF-IL 6：）以及它们如何与盲肠结扎和穿孔（CLP）的鼠模型中的促炎细胞因子表达和死亡率相关。CLP诱导多菌性脓毒症模型，采用电泳迁移率改变法检测CLP后0、1、2、3、4、5、6、8和24 h转录因子的活化情况，结果：CLP诱导肺组织NF κ B B活化，在3、4、8、10、12、14、18、19、20、21、30、40、60、70、80、90、100、10 8小时组与对照组比较差异有显著性（P < 0.05）。肺NF κ B活化在3小时达到峰值（533%对比无手术，2,900%对比假手术），Supershift分析显示CLP后3小时脓毒症小鼠的肺核提取物中p50亚基占优势，表明存在p50同源二聚体。相反，脓毒症小鼠的肝细胞核提取物表明在3小时时存在p65和p50亚基，肺NF-IL 6活化在CLP后4小时（649% vs.无手术，296% vs.假治疗）和6小时观察到（p < 0.05）。CLP后各时间点肺肿瘤坏死因子-α mRNA水平均升高（p < 0.05）。CLP后3、6、8 h肺组织IL-6 mRNA水平升高。结论：多菌败血症早期肺组织NF-κ B、NF-IL-6活化及细胞因子mRNA表达与死亡率相关。虽然IL-6 mRNA水平与NF κ B B和NF-IL 6活化相关，但肿瘤坏死因子-α mRNA水平与之无关，因为它们先于转录因子活化。这些数据表明NF κ B B和NF-IL 6活化在急性肺损伤的起始和传播中的潜在作用。
Background: Transcription factor activation may be a pivotal step in the pathophysiology of sepsis syndrome and adult respiratory distress syndrome. This study investigated the activation of lung nuclear factor kappa B (NF kappa B) and nuclear factor interleukin-6 (NF-IL6:) and how they correlate to proinflammatory cytokine expression and mortality in a murine model of cecal ligation and puncture (CLP),Methods: Polymicrobial sepsis was induced by CLP, Transcription factor activation was assessed at 0, 1, 2, 3, 4, 5, 6, 8, and 24 hours after CLP by the electrophoretic mobility-shift assay, Lung cytokine mRNA levels were established by reverse transcriptase-polymerase chain reaction,Results: CLP induced pulmonary NF kappa B activation at 3, 4. and 8 hours (p < 0.05). Lung NF kappa B activation peaked at 3 hours (533% vs. no surgery, 2,900% vs. sham treatment) after CLP, Supershift analysis revealed a predominance of p50 subunits in the lung nuclear extracts of septic mice 3 hours after CLP, indicating the presence of p50 homodimer, In contrast, liver nuclear extracts from septic mice indicated the presence of both p65 and p50 subunits at 3 hours, Lung NF-IL6 activation (p < 0.05) was observed at 4 hours (649% vs. no surgery, 296% vs, sham treatment) and 6 hours after CLP. Lung tumor necrosis factor-alpha mRNA levels were increased (p < 0.05) at all time interval after CLP. Lung IL-6 mRNA levels were increased at 3, 6, and 8 hours after CLP.Conclusion: Early activation of lung NF kappa B and NF-IL6 and lung cytokine mRNA expression correlated with mortality in polymicrobial sepsis. Although IL-6 mRNA levels correlated with NF kappa B and NF-IL6 activation, tumor necrosis factor-alpha mRNA levels did not, in that they preceded transcription factor activation, These data suggest a potential role for NF kappa B and NF-IL6 activation in the initiation and propagation of acute lung injury.