The production of endothelin-1 (ET-1) by macrophages during infection and inflamm

感染和炎症期间巨噬细胞产生内皮素-1 (ET-1)

• 批准号: 6952510
• 负责人: ANDREW BRITTINGHAM
• 金额: $ 18.03万
• 依托单位: DES MOINES UNIV OSTEOPATHIC MEDICAL CTR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-25 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6952510
• 关键词: DNA binding protein; biological signal transduction; endothelin; infection; inflammation; laboratory mouse; ligands; macrophage; polymerase chain reaction; protein protein interaction; receptor; toll like receptor; vascular smooth muscle; vasoconstrictors

DESCRIPTION (provided by applicant): The purpose of this study is to gain a better understanding of the source, function, and cause of the elevated levels of Endothelin-1 (ET-1) observed during infection and inflammation. Initially described as a potent vascular smooth muscle constrictor released from the endothelium by ischemia, injury, or inflammation, ET-1 is now known to be produced by a variety of cells and tissues under normal and pathological conditions. Elevated levels of ET-1 are observed during and may contribute to the pathology of a number of localized and systemic inflammatory conditions including atherosclerosis, asthma, and sepsis. While the importance of ET-1 for normal cardiovascular development during embryogenesis and cardiovascular function in the adult is widely accepted, the importance of ET-1 during these inflammatory conditions is only beginning to emerge. Clinical and experimental studies have identified macrophages as a potential source of ET-1 during infection and inflammation. Studies outlined in this proposal are designed to characterize the production of endothelin- 1 (ET-1) by macrophages in response to microbial challenge. We propose to identify receptor-ligand interactions, cell signaling events, and cis- and trans-acting factors which regulate the production of ET-1 by macrophages. We hypothesize that ET-1 production is part of the characteristic macrophage response to microbial challenge and that macrophages are a key source of ET-1 during infection and inflammation. Macrophage derived ET-1 has the potential to affect tissue perfusion, angiogenesis, atherogenesis, leukocyte extravasation, and immune cell function. An understanding of how ET-1 production is regulated during pathological states, and how this differs from its normal physiological production, may allow for the design of specific therapeutic interventions which can harness its aberrant production without disrupting its normal physiological activities.

描述（由申请人提供）：本研究的目的是为了更好地了解感染和炎症期间观察到的内皮素-1 （ET-1）水平升高的来源、功能和原因。

项目成果

Endothelin-1 production by the canine macrophage cell line DH82: enhanced production in response to microbial challenge.

犬巨噬细胞系 DH82 产生内皮素-1：响应微生物挑战而增强产量。

• DOI: 10.1016/j.vetimm.2010.02.006
• 发表时间: 2010
• 期刊: Veterinary immunology and immunopathology
• 影响因子: 1.8
• 作者: Divino,JeffreyN;Chawla,KashmiraS;daSilva,ChristinaM;Bjorge,AshleyM;Brittingham,Andrew
• 通讯作者: Brittingham,Andrew