TNF 的凝集素样结构域可防止李斯特菌溶血素诱导的人肺微血管内皮细胞过度通透 - 蛋白激酶 C-α抑制的关键作用。
The lectin-like domain of TNF protects from listeriolysin-induced hyperpermeability in human pulmonary microvascular endothelial cells - a crucial role for protein kinase C-alpha inhibition.
机构信息
Medical College of Georgia, Augusta, GA, USA.
出版信息
Vascul Pharmacol. 2010 May-Jun;52(5-6):207-13. doi: 10.1016/j.vph.2009.12.010. Epub 2010 Jan 13.
Abstract
Listeriosis can lead to potentially lethal pulmonary complications in newborns and immune compromised patients, characterized by extensive permeability edema. Listeriolysin (LLO), the main virulence factor of Listeria monocytogenes, induces a dose-dependent hyperpermeability in monolayers of human lung microvascular endothelial cells in vitro. The permeability increasing activity of LLO, which is accompanied by an increased reactive oxygen species (ROS) generation, RhoA activation and myosin light chain (MLC) phosphorylation, can be completely inhibited by the protein kinase C (PKC) alpha/beta inhibitor GO6976, indicating a crucial role for PKC in the induction of barrier dysfunction. The TNF-derived TIP peptide, which mimics the lectin-like domain of the cytokine, blunts LLO-induced hyperpermeability in vitro, upon inhibiting LLO-induced protein kinase C-alpha activation, ROS generation and MLC phosphorylation and upon restoring the RhoA/Rac 1 balance. These results indicate that the lectin-like domain of TNF has a potential therapeutic value in protecting from LLO-induced pulmonary endothelial hyperpermeability.
摘要
李斯特菌病可导致新生儿和免疫功能低下患者出现潜在致命性的肺部并发症，其特征为广泛通透性水肿。李斯特菌溶血素（LLO）是单核细胞增生李斯特菌的主要毒力因子，可在体外诱导人肺微血管内皮细胞单层的剂量依赖性高通透性。LLO 的通透性增加活性伴随着活性氧（ROS）生成、RhoA 激活和肌球蛋白轻链（MLC）磷酸化的增加，可被蛋白激酶 C（PKC）α/β抑制剂 GO6976 完全抑制，表明 PKC 在诱导屏障功能障碍中起关键作用。源自 TNF 的 TIP 肽模拟细胞因子的凝集素样结构域，在体外抑制 LLO 诱导的通透性增加，抑制 LLO 诱导的蛋白激酶 C-α激活、ROS 生成和 MLC 磷酸化，并恢复 RhoA/Rac1 平衡。这些结果表明 TNF 的凝集素样结构域在保护李斯特菌诱导的肺内皮通透性增加方面具有潜在的治疗价值。
相似文献
1
The lectin-like domain of TNF protects from listeriolysin-induced hyperpermeability in human pulmonary microvascular endothelial cells - a crucial role for protein kinase C-alpha inhibition.TNF 的凝集素样结构域可防止李斯特菌溶血素诱导的人肺微血管内皮细胞过度通透 - 蛋白激酶 C-α抑制的关键作用。
Vascul Pharmacol. 2010 May-Jun;52(5-6):207-13. doi: 10.1016/j.vph.2009.12.010. Epub 2010 Jan 13.
2
Listeriolysin O Causes ENaC Dysfunction in Human Airway Epithelial Cells.李斯特菌溶血素 O 导致人呼吸道上皮细胞 ENaC 功能障碍。
Toxins (Basel). 2018 Feb 11;10(2):79. doi: 10.3390/toxins10020079.
3
RhoA and Rho-kinase dependent and independent signals mediate TGF-beta-induced pulmonary endothelial cytoskeletal reorganization and permeability.RhoA和Rho激酶依赖性及非依赖性信号介导转化生长因子-β诱导的肺内皮细胞骨架重组和通透性。
Am J Physiol Lung Cell Mol Physiol. 2005 Feb;288(2):L294-306. doi: 10.1152/ajplung.00213.2004. Epub 2004 Oct 8.
4
Human endothelial cell activation and mediator release in response to Listeria monocytogenes virulence factors.人类内皮细胞对单核细胞增生李斯特菌毒力因子的激活及介质释放反应。
Infect Immun. 2001 Feb;69(2):897-905. doi: 10.1128/IAI.69.2.897-905.2001.
5
Protein kinase C-α and arginase I mediate pneumolysin-induced pulmonary endothelial hyperpermeability.蛋白激酶 C-α 和精氨酸酶 I 介导肺炎球菌溶血素诱导的肺血管内皮通透性增加。
Am J Respir Cell Mol Biol. 2012 Oct;47(4):445-53. doi: 10.1165/rcmb.2011-0332OC. Epub 2012 May 10.
6
Heat shock protein 90 inhibitors prevent LPS-induced endothelial barrier dysfunction by disrupting RhoA signaling.热休克蛋白 90 抑制剂通过破坏 RhoA 信号通路来防止 LPS 诱导的内皮屏障功能障碍。
Am J Respir Cell Mol Biol. 2014 Jan;50(1):170-9. doi: 10.1165/rcmb.2012-0496OC.
7
Rho and ROCK signaling in VEGF-induced microvascular endothelial hyperpermeability.Rho和ROCK信号传导在血管内皮生长因子诱导的微血管内皮细胞高通透性中的作用
Microcirculation. 2006 Apr-May;13(3):237-47. doi: 10.1080/10739680600556944.
8
RhoA S-nitrosylation as a regulatory mechanism influencing endothelial barrier function in response to G-bacterial toxins.RhoA亚硝基化作为一种调节机制，影响内皮细胞屏障功能以响应革兰氏阴性细菌毒素。
Biochem Pharmacol. 2017 Mar 1;127:34-45. doi: 10.1016/j.bcp.2016.12.014. Epub 2016 Dec 22.
9
S-1-propenylcysteine improves TNF-α-induced vascular endothelial barrier dysfunction by suppressing the GEF-H1/RhoA/Rac pathway.S-1-丙烯基半胱氨酸通过抑制 GEF-H1/RhoA/Rac 通路改善 TNF-α 诱导的血管内皮屏障功能障碍。
Cell Commun Signal. 2021 Feb 15;19(1):17. doi: 10.1186/s12964-020-00692-w.
10
Differential regulation of TNF-alpha production by listeriolysin-producing versus nonproducing strains of Listeria monocytogenes.产李斯特菌溶素的单核细胞增生李斯特菌菌株与不产该溶素的菌株对肿瘤坏死因子-α 产生的差异调节
J Leukoc Biol. 1995 Nov;58(5):556-62. doi: 10.1002/jlb.58.5.556.
引用本文的文献
1
The pathogenesis and management of heatstroke and heatstroke-induced lung injury.中暑及中暑诱导性肺损伤的发病机制与治疗
Burns Trauma. 2025 Jan 14;13:tkae048. doi: 10.1093/burnst/tkae048. eCollection 2025.
2
The Epithelial Sodium Channel-An Underestimated Drug Target.上皮钠离子通道：一个被低估的药物靶点。
Int J Mol Sci. 2023 Apr 24;24(9):7775. doi: 10.3390/ijms24097775.
3
The SARS-CoV-2 spike S1 protein induces global proteomic changes in ATII-like rat L2 cells that are attenuated by hyaluronan.SARS-CoV-2 刺突蛋白 S1 诱导类似于 ATII 的大鼠 L2 细胞中的全蛋白质组变化，透明质酸可减弱这种变化。
Am J Physiol Lung Cell Mol Physiol. 2023 Apr 1;324(4):L413-L432. doi: 10.1152/ajplung.00282.2022. Epub 2023 Jan 31.
4
Dichotomous Role of Tumor Necrosis Factor in Pulmonary Barrier Function and Alveolar Fluid Clearance.肿瘤坏死因子在肺屏障功能和肺泡液体清除中的双重作用
Front Physiol. 2022 Feb 21;12:793251. doi: 10.3389/fphys.2021.793251. eCollection 2021.
5
Hsp70 Suppresses Mitochondrial Reactive Oxygen Species and Preserves Pulmonary Microvascular Barrier Integrity Following Exposure to Bacterial Toxins.热休克蛋白70抑制线粒体活性氧，并在暴露于细菌毒素后维持肺微血管屏障完整性。
Front Immunol. 2018 Jun 12;9:1309. doi: 10.3389/fimmu.2018.01309. eCollection 2018.
6
Listeriolysin O Causes ENaC Dysfunction in Human Airway Epithelial Cells.李斯特菌溶血素 O 导致人呼吸道上皮细胞 ENaC 功能障碍。
Toxins (Basel). 2018 Feb 11;10(2):79. doi: 10.3390/toxins10020079.
7
Cytokine-Ion Channel Interactions in Pulmonary Inflammation.肺部炎症中的细胞因子-离子通道相互作用
Front Immunol. 2018 Jan 4;8:1644. doi: 10.3389/fimmu.2017.01644. eCollection 2017.
8
Epithelial Sodium Channel-α Mediates the Protective Effect of the TNF-Derived TIP Peptide in Pneumolysin-Induced Endothelial Barrier Dysfunction.上皮钠通道-α介导肿瘤坏死因子衍生的TIP肽对肺炎溶血素诱导的内皮屏障功能障碍的保护作用。
Front Immunol. 2017 Jul 21;8:842. doi: 10.3389/fimmu.2017.00842. eCollection 2017.
9
Inhaled AP301 for treatment of pulmonary edema in mechanically ventilated patients with acute respiratory distress syndrome: a phase IIa randomized placebo-controlled trial.吸入 AP301 治疗机械通气急性呼吸窘迫综合征患者肺水肿：一项 IIa 期随机安慰剂对照试验。
Crit Care. 2017 Jul 27;21(1):194. doi: 10.1186/s13054-017-1795-x.
10
TNF Lectin-Like Domain Restores Epithelial Sodium Channel Function in Frameshift Mutants Associated with Pseudohypoaldosteronism Type 1B.肿瘤坏死因子凝集素样结构域可恢复与1B型假性醛固酮减少症相关的移码突变体中的上皮钠通道功能。
Front Immunol. 2017 May 29;8:601. doi: 10.3389/fimmu.2017.00601. eCollection 2017.
本文引用的文献
1
The lectin-like domain of tumor necrosis factor improves lung function after rat lung transplantation--potential role for a reduction in reactive oxygen species generation.肿瘤坏死因子的凝集素样结构域改善大鼠肺移植后的肺功能--减少活性氧生成的潜在作用。
Crit Care Med. 2010 Mar;38(3):871-8. doi: 10.1097/CCM.0b013e3181cdf725.
2
Regulators of endothelial and epithelial barrier integrity and function in acute lung injury.急性肺损伤中内皮和上皮屏障完整性及功能的调节因子。
Biochem Pharmacol. 2009 Jun 15;77(12):1763-72. doi: 10.1016/j.bcp.2009.01.014. Epub 2009 Feb 3.
3
Functional ENaC channels expressed in endothelial cells: a new candidate for mediating shear force.内皮细胞中表达的功能性上皮钠通道：介导剪切力的新候选者。
Microcirculation. 2009 Apr;16(3):276-87. doi: 10.1080/10739680802653150. Epub 2009 Feb 16.
4
Structural basis of protein kinase C isoform function.蛋白激酶C同工型功能的结构基础。
Physiol Rev. 2008 Oct;88(4):1341-78. doi: 10.1152/physrev.00034.2007.
5
The lectin-like domain of tumor necrosis factor-alpha improves alveolar fluid balance in injured isolated rabbit lungs.肿瘤坏死因子-α的凝集素样结构域可改善离体损伤兔肺的肺泡液体平衡。
Crit Care Med. 2008 May;36(5):1543-50. doi: 10.1097/CCM.0b013e31816f485e.
6
Regulation of endothelial junctional permeability.内皮细胞连接通透性的调节。
Ann N Y Acad Sci. 2008 Mar;1123:134-45. doi: 10.1196/annals.1420.016.
7
Differential roles of PKCalpha and PKCepsilon in controlling the gene expression of Nox4 in human endothelial cells.蛋白激酶Cα（PKCα）和蛋白激酶Cε（PKCε）在调控人内皮细胞中Nox4基因表达方面的不同作用。
Free Radic Biol Med. 2008 Apr 15;44(8):1656-67. doi: 10.1016/j.freeradbiomed.2008.01.023. Epub 2008 Feb 7.
8
Aldosterone and amiloride alter ENaC abundance in vascular endothelium.醛固酮和氨氯吡咪可改变血管内皮细胞中上皮钠通道（ENaC）的丰度。
Pflugers Arch. 2008 Feb;455(5):849-57. doi: 10.1007/s00424-007-0341-0. Epub 2007 Sep 22.
9
Hypoxia-dependent regulation of nonphagocytic NADPH oxidase subunit NOX4 in the pulmonary vasculature.肺血管中非吞噬性NADPH氧化酶亚基NOX4的缺氧依赖性调控
Circ Res. 2007 Aug 3;101(3):258-67. doi: 10.1161/CIRCRESAHA.107.148015. Epub 2007 Jun 21.
10
The multiple mechanisms of Ca2+ signalling by listeriolysin O, the cholesterol-dependent cytolysin of Listeria monocytogenes.单核细胞增生李斯特菌的胆固醇依赖细胞溶素——溶血素O介导Ca2+信号传导的多种机制
Cell Microbiol. 2007 Aug;9(8):2008-21. doi: 10.1111/j.1462-5822.2007.00932.x. Epub 2007 Apr 5.
Zotero 插件