Platelet-activating factor induces the processing of nuclear factor-κB p105 into p50, which mediates acute bowel injury in mice
Platelet-activating factor induces the processing of nuclear factor-κB p105 into p50, which mediates acute bowel injury in mice
复制标题
DOI：
10.1152/ajpgi.00053.2009
复制
发表时间：
2009-07-01
影响因子：
4.5
通讯作者：
De Plaen, Isabelle G.
中科院分区：
文献类型：
--
作者：
Liu, Shirley X. L.;Tian, Runlan;De Plaen, Isabelle G.
刘SXL，田R，Baskind H，Hsueh W，De Plaen IG。血小板激活因子诱导核因子 kappa B p105 加工成 p50，从而介导小鼠急性肠损伤。 Am J Physiol Gastrointest Liver Physiol 297：G76-G81，2009。首次发表于 2009 年 5 月 21 日； doi:10.1152/ajpgi.00053.2009.-血小板激活因子 (PAF) 是一种内源性促炎磷脂，当血管内注射到大鼠和小鼠时，会引起休克、急性肠损伤，并快速激活 NF-κ B p50-p50，同时上调肠道内趋化因子 CXCL2。在本研究中，我们研究了 NF-kappa B 激活的机制以及 NF-kappa B p50 亚基在 PAF 诱导的休克和急性肠损伤中的作用。将 NF-kappa B p50 缺陷型小鼠和野生型小鼠麻醉并切开气管，在其颈动脉中插管以监测血压、采血和施用 PAF。为了测定肠损伤、休克和存活率，注射 PAF（2.2 μg/kg，动脉内注射）。两小时后，对动物实施安乐死，取出小肠进行组织学检查。对于生化研究，施用 PAF（1.5 μg/kg i.a.）并在 15-60 分钟后取出小肠。我们发现 PAF 在 30 分钟内诱导 p105 加工增加，但 NF-kappa B 抑制蛋白 I kappa B α 和 β 的水平没有变化。与野生型动物相比，NF-kappa B p50 缺陷小鼠可以免受 PAF 诱导的死亡、休克、肠道灌注不足和损伤。我们还发现，与野生型小鼠相比，p50 缺陷小鼠的 CXCL2 和 TNF 基因表达降低，CXCL2 蛋白产量减少。我们的研究表明，PAF 增加了 NF-kappa B p105 向 p50 的加工，并上调促炎细胞因子，从而导致 PAF 诱导的全身炎症反应和急性肠损伤。
Liu SXL, Tian R, Baskind H, Hsueh W, De Plaen IG. Platelet-activating factor induces the processing of nuclear factor-kappa B p105 into p50, which mediates acute bowel injury in mice. Am J Physiol Gastrointest Liver Physiol 297: G76-G81, 2009. First published May 21, 2009; doi:10.1152/ajpgi.00053.2009.-Platelet-activating factor (PAF), an endogenous proinflammatory phospholipid, when injected intravascularly to rats and mice, causes shock, acute bowel injury, and a rapid activation of NF-kappa B p50-p50 with upregulation of the chemokine CXCL2 in the intestine. In this study, we investigate the mechanism of NF-kappa B activation and the role of the NF-kappa B p50 subunit in PAF-induced shock and acute bowel injury. NF-kappa B p50-deficient mice and wild-type mice were anesthetized and tracheotomized, and their carotid artery was cannulated for blood pressure monitoring, blood sampling, and PAF administration. For determination of bowel injury, shock, and survival, PAF (2.2 mu g/kg, intraarterially, i.a.) was injected. Two hours later, animals were euthanized, and their small intestines were removed for histological examination. For biochemical studies, PAF (1.5 mu g/kg i.a.) was administered and the small intestine removed after 15-60 min. We found that PAF induced an increase in p105 processing within 30 min, but there were no changes in the levels of the NF-kappa B inhibitory proteins I kappa B alpha and beta. NF-kappa B p50-deficient mice were protected against PAF-induced mortality, shock, intestinal hypoperfusion, and injury compared with wild-type animals. We also found that p50-deficient mice had decreased gene expression of CXCL2 and TNF and a decrease in CXCL2 protein production compared with wild-type mice. Our study suggests that PAF increases the processing of NF-kappa B p105 into p50, with upregulation of proinflammatory cytokines, which leads to PAF-induced systemic inflammatory response and acute bowel injury.