Liver Lung Interactions in Lung Inflammation

肺部炎症中肝肺的相互作用

• 批准号: 6998889
• 负责人: BRIAN W CHRISTMAN
• 金额: $ 177.15万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6998889
• 关键词: cytokine; inflammation; liver disorder; lung injury; oxidative stress

It is abundantly clear from both experimental observations and clinical experience, that interactions between the liver and the lungs can play a critical role in the initiation and outcome of lung inflammation. We propose a Program Project consisting of four inter-related projects and three core areas to investigate mechanisms of interactions between the liver and the lungs in acute lung injury syndromes. The underlying theme, addressed in different by each of the projects, is that hepatic injury, whether resulting from endotoxemia, direct trauma or drug injury, can signal an inflammatory response in the lungs that may eventuate in acute lung injury and that eicosanoids play a critical role in modulating that process. Pro-inflammatory cytokines, including tumor necrosis factor alpha, produced in the liver, comprise the liver inflammatory signal. Activation of two transcription factors, nuclear factor kappa B (NFkB) and CCAAT enhancer binding protein beta (C/EBPbeta a.k.a. NF-IL6) is critical to the response in the lungs and in the liver and the course of the response of the lungs to liver injury is determined by the pattern of activation of these two factors. Oxidant stress is common to many causes of hepatic injury and abnormalities in function of the hepatic urea cycle exaggerate oxidant stress resulting in enhanced activation of transcription factors and thus cytokine release, amplifying the inflammatory signal to the lungs. The program forms a structural basis for enhancing previous and existing collaborations among investigators from Pulmonary Medicine, Surgery, Pediatrics, Pharmacology, Biochemistry, Microbiology and Immunology and Molecular Physiology and Biophysics. The program as a whole will integrate the pathophysiology of lung injury with biochemical cellular and molecular mechanisms of liver-lung relationships that contribute to or moderate the inflammatory response. Experimental approaches include whole animal physiologic preparations as well as numerous genetically altered mouse models and bone marrow and hepatocyte transplantation technology as experimental tools. The proposal promises to obtain new information related to mechanisms of lung injury which will be clinically relevant by providing rationales for new preventive or therapeutic strategies as well as the ability to identity at risk individuals The proposal results from the conviction by the involved investigators that the common themes, complementary expertise and unique technologies assembled into a coordinated program will be more creative, more productive and more likely ti advance understanding of the pathogenesis and potential therapy of inflammatory lung disease.

从实验观察和临床经验中可以清楚地看出，肝脏和肺之间的相互作用在肺部炎症的起始和结局中起着至关重要的作用。我们提出了一个计划项目，该项目由四个相互关联的项目和三个核心领域组成，以研究急性肺损伤综合征中肝脏与肺之间相互作用的机制。每个项目都在不同的项目中解决的基本主题是，肝损伤，无论是由内毒素血症，直接创伤还是药物损伤引起的，都可以指示肺部可能在急性肺损伤中发生的炎症反应，而类糖酸在调节这一过程中起着至关重要的作用。肝脏中产生的促炎细胞因子，包括肿瘤坏死因子α，包括肝脏炎症信号。激活两个转录因子Kappa B（NFKB）和CCAAT增强子结合蛋白β（C/EBPBETA又称NF-IL6）的激活对肺和肝脏中的反应至关重要，以及通过这两种因素的激活模式确定肺对肝脏损伤的反应。氧化应激是肝损伤的许多原因和肝尿素周期功能异常的常见，从而夸大了氧化剂应激，从而增强了转录因子的激活，从而释放了细胞因子，从而扩大了炎症信号向肺部。该计划构成了结构性的基础，以增强肺部医学，手术，儿科，药理学，生物化学，微生物学和免疫学以及分子生理学和生物物理学的研究人员之间的以前和现有合作。该程序整体将使肺损伤的病理生理与肝肺关系的生化细胞和分子机制相结合，从而有助于或缓解炎症反应。实验方法包括整个动物生理制剂，以及许多遗传改变的小鼠模型，骨髓和肝细胞移植技术作为实验工具。该提案有望获得与肺损伤机制有关的新信息，通过为新的预防或治疗策略提供理由以及在风险个人身份认同的能力中，这些信息将在临床上相关，并能够使所涉及的调查人员的信念所产生的提案所导致的提案所导致的普通主题，即常见的主题，互补的专业技术和更具创造性的技术，并具有更有创造力的技术，并且具有更有创造力的效果，并且有效性地构成了TIV，并且有效性地提高了TII，并且有效性地提高了TII，并具有更大的作用。炎症性肺部疾病。

项目成果

Protective role of bortezomib in steatotic liver ischemia/reperfusion injury through abrogation of MMP activation and YKL-40 expression.

• DOI: 10.1016/j.trim.2013.12.003
• 发表时间: 2014-03
• 期刊: Transplant immunology
• 影响因子: 1.5
• 作者: Tiriveedhi V;Upadhya GA;Busch RA;Gunter KL;Dines JN;Knolhoff BL;Jia J;Sarma NJ;Ramachandran S;Anderson CD;Mohanakumar T;Chapman WC
• 通讯作者: Chapman WC

Inhibitory kappaB kinase 2 activates airway epithelial cells to stimulate bone marrow macrophages.

• DOI: 10.1165/rcmb.2006-0245oc
• 发表时间: 2007-01
• 期刊: American journal of respiratory cell and molecular biology
• 影响因子: 6.4
• 作者: B. Mathew;G. Park;H. Cao;A. Azim;Xuerong Wang;R. V. van Breemen;R. Sadikot;J. Christman

Conditional regulation of cyclooxygenase-2 in tracheobronchial epithelial cells modulates pulmonary immunity.

气管支气管上皮细胞中环氧合酶-2 的条件调节可调节肺部免疫。

• DOI: 10.1111/j.1365-2249.2007.03478.x
• 发表时间: 2007
• 期刊: Clinical and experimental immunology
• 影响因子: 4.6
• 作者: Park,GY;Hu,N;Wang,X;Sadikot,RT;Yull,FE;Joo,M;PeeblesJr,RS;Blackwell,TS;Christman,JW
• 通讯作者: Christman,JW