Hepatic gene expression and cytokine responses to sterile inflammation: Comparison with cecal ligation and puncture sepsis in the rat
Hepatic gene expression and cytokine responses to sterile inflammation: Comparison with cecal ligation and puncture sepsis in the rat
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DOI：
10.1097/00024382-199905000-00008
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发表时间：
1999-05-01
期刊：
影响因子：
3.1
通讯作者：
Deutschman, CS
中科院分区：
文献类型：
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作者：
Bazel, S;Andrejko, KM;Deutschman, CS
肝脏急性期蛋白表达的炎症刺激部分受肿瘤坏死因子-α（TNF α）、白细胞介素-1 β（IL-1 β）和IL-6调节。这些细胞因子也可能介导脓毒症的持续性炎症和代谢失调的某些方面。雄性Sprague-Dawley大鼠盲肠结扎穿孔（CLP）脓毒症不适当地降低了磷酸烯醇式丙酮酸羧激酶（PEPCK）、葡萄糖-6-磷酸酶（G6 β）、肉毒碱棕榈酰转移酶II（CPTII）、乙酰辅酶A酰基转移酶（ACA）和鸟氨酸转氨甲酰酶（OTC）的肝细胞转录。我们假设：1）皮下注射turtum诱导的简单炎症后不会发生转录重编程，2）CLP后急性期基因表达模式与turtum注射后不同，3）不同的反应反映了TNF α/IL-1 β或IL-6肝内活性的差异。基因表达，转录因子的活性，和细胞因子的丰度后，无论是皮下注射turpestine或CLP确定。在注射turtectin后，PEPCK、G6 β、CPTII、ACA和OTC表达没有变化，与先前报道的CLP后的数据不同。姜黄素注射液和CLP均可增加TNF α/IL-1 β调节的α 1-酸性糖蛋白和IL-6调节的α 2-巨球蛋白的表达，并降低甲状腺素运载蛋白（一种阴性急性期蛋白）的表达。然而，表达的幅度和时间模式不同。Turnover注射增加了TNF α/IL-1 β-连接的转录因子NF-κ B的活性和肝内TNF α的丰度，其方式与CLP后观察到的相似，但仅轻微改变了IL-6-连接的转录因子Stat-3的活性和肝内IL-6的丰度。这与CLP后的观察结果显著不同。我们的结论是，CLP诱导的肝脏基因表达的改变可能反映了IL-6活性的差异。
Inflammatory stimulation of hepatic acute phase protein expression is, in part, modulated by tumor necrosis factor-alpha (TNF alpha), interleukin-1 beta (IL-1 beta), and IL-6. These cytokines also may mediate some aspects of the persistent inflammation and metabolic dysregulation of sepsis. Cecal ligation and puncture (CLP) sepsis in male Sprague-Dawley rats inappropriately decreases hepatocellular transcription of phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), carnitine palmitoyltransferase II (CPTII), acetyl CoA acyltransferase (ACA), and ornithine transcarbamylase (OTC). We hypothesize that 1) transcriptional reprogramming does not occur after simple inflammation induced by subcutaneous turpentine injection, 2) the pattern of acute phase gene expression after CLP differs from that following turpentine injection, and 3) the different responses reflect differences in the intrahepatic activity of TNF alpha/IL-1 beta or IL-6. Gene expression, transcription factor activity, and cytokine abundance were determined after either a subcutaneous injection of turpentine or CLP. After turpentine injection, PEPCK, G6Pase, CPTII, ACA, and OTC expression were unchanged, different from previously reported data following CLP. Both turpentine injection and CLP increased expression of TNF alpha/IL-1 beta-regulated alpha(1)-acid glycoprotein, and IL-6-regulated alpha(2)-macroglobulin and decreased expression of transthyretin (a negative acute phase protein). However, the magnitude and temporal pattern of expression differed. Turpentine injection increased the activity of the TNF alpha/IL-1 beta-linked transcription factor NF-kappa B and the intrahepatic abundance of TNF alpha in a manner similar to that observed after CLP but only slightly altered the activity of the IL-6-linked transcription factor Stat-3 and intrahepatic IL-6 abundance. This differed significantly from observations after CLP. We conclude that CLP-induced alterations in hepatic gene expression may reflect differences in IL-6 activity.