Regulation of Cortisol by Mycobacterial Glycolipid TDM

分枝杆菌糖脂 TDM 对皮质醇的调节

• 批准号: 6719381
• 负责人: JEFFREY K ACTOR
• 金额: $ 18.19万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-23 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6719381
• 关键词: Mycobacterium; cortisol; dehydroepiandrosterone; enzyme linked immunosorbent assay; glucocorticoids; glycolipids; histology; immune response; immunopathology; immunoregulation; interleukin 6; laboratory mouse; morphometry; polymerase chain reaction; psychoneuroimmunology; pulmonary fibrosis /granuloma; serum; trehalose; tuberculosis; tumor necrosis factor alpha

DESCRIPTION (provided by applicant): The observation of glucocorticoid modulation during tuberculosis infection has been known for many years, however the relationship between glucocorticoid immunomodulation and destructive pathological and granulomatous responses to mycobacterial antigens remains poorly understood. Indeed, relative amounts of both systemic and tissue specific cortisol may be crucial in susceptibility to tuberculosis, and therefore play a defining role in ensuing pathology. C57BL/6 mice demonstrate a rapid decrease in serum cortisol levels during initiation of granulomatous response during acute experimental infection with virulent Mycobacterium tuberculosis. Investigators have actively pursued agents that mimic immunopathology associated with tuberculosis. One such agent; the natural mycobacterial glycolipid trehalose 3,6'dimycolate (TDM) has been researched extensively as a mediator of biological events and granulomatous responses during disease. We have further identified mycobacterial TDM as able to influence systemic serum cortisol levels. This is the first observation of mediation of a systemic glucocorticoid to a mycobacterial glycolipid, and warrants further investigation. Our preliminary findings indicate a need to explore the influence of cortisol on initial events involved in the immunoregulation and immunopathology due to mycobacterial glycolipid TDM. The goal of this application is therefore to examine the relationship between immune- responses induced by mycobacterial glycolipid and associated concurrent imbalances in both serum and tissue glucocorticoids (cortisol) during development of the pulmonary granulomatous response. We request that this proposal be considered for R21 funding directed towards exploratory research into applications of physioneuroimmunology towards understanding the basis of immunoregulated disease pathology during tuberculosis infection.

描述（由申请人提供）：在结核病感染期间糖皮质激素调节的观察已知多年了，但是糖皮质激素免疫调节与破坏性病理学和肉芽肿对分枝杆菌抗原的反应之间的关系仍然很少。实际上，系统性和组织特异性皮质醇的相对量对于对结核病的敏感性可能至关重要，因此在病理学中起着决定性作用。 C57BL/6小鼠在急性实验感染过程中伴有毒性分枝杆菌的急性实验感染期间，血清皮质醇水平迅速降低。研究人员积极追求模仿与结核病相关的免疫病理学的药物。一个这样的代理人；天然的分枝杆菌糖脂三核3,6'Dimycaly（TDM）已被广泛研究为疾病期间生物事件和肉芽肿反应的中介。我们进一步确定了分枝杆菌TDM能够影响系统性血清皮质醇水平。这是对分枝杆菌糖脂的全身性糖皮质激素介导的首次观察，并需要进一步研究。 我们的初步发现表明，有必要探索皮质醇对分枝杆菌糖脂TDM引起的免疫调节和免疫病理学涉及的初始事件的影响。因此，该应用的目的是检查分枝杆菌糖脂引起的免疫反应与血清和组织糖皮质激素（皮质醇）在肺肉芽肿反应过程中的同时失衡之间的关系。我们要求考虑该建议用于用于探索性研究的R21资金，以研究生理学免疫学对理解结核病感染期间免疫调节疾病病理学的基础的应用。