TGF BETA FOLLOWING BURN INJURY

烧伤后的 TGF Beta

• 批准号: 2185699
• 负责人: RICHARD A WINCHURCH
• 金额: $ 12.72万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-01 至 1995-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2185699
• 关键词: blood chemistry; burns; endotoxins; enzyme linked immunosorbent assay; growth factor receptors; human subject; immunosuppression; interleukin 6; lymphocyte proliferation; messenger RNA; monoclonal antibody; monocyte; northern blottings; nucleic acid hybridization; receptor expression; transforming growth factors

Burn injury suppresses immunity and this suppression is reflected in aberrations of the cellular composition and regulatory cytokine levels of the immune system. One of the major causes of immune dysfunction following injury is an increase in circulating endotoxin but the mechanisms by which endotoxin produces its effects remain unclear. Studies of burn victims have shown that the injury is associated with high increases in endotoxin- induced interleukin 6. These pathophysiologic levels of Il-6 have been recently shown to induce increases in the activity of transforming growth factor beta (TGF beta), a potent suppressor of immune functions. The overall goal of this project is to evaluate the role of TGF beta in the immunosuppression of burn patients. These studies will include quantitation of the plasma levels of TGF beta, analysis of TGF beta mRNA synthesis in peripheral mononuclear cells, evaluation of the relationships between the immunosuppressive properties of burn serum and TGF beta activity, an examination of the ability of Il-6 to induce increases of TGF beta and the study of TGF beta receptor expression on peripheral blood mononuclear cells. Finally, we will study possible mechanisms by which TGF beta inhibits lymphocyte proliferation with primary studies directed toward an assessment of the effects of TGF beta on the major genes known to be involved in lymphocyte proliferative responses.

烧伤损伤抑制免疫，这种抑制反映在 细胞组成和调节细胞因子水平的畸变 免疫系统。 免疫功能障碍的主要原因之一 损伤是循环内毒素的增加，但其机制是 内毒素产生其作用尚不清楚。 烧伤受害者的研究 已经表明，损伤与内毒素 - 高增加有关 诱导的白介素6。这些IL-6的病理生理水平已经 最近显示的可引起变化活性的增加 因子β（TGF Beta），一种有效的免疫功能抑制剂。 该项目的总体目标是评估TGF Beta在 烧伤患者的免疫抑制。 这些研究将包括 TGFβ的血浆水平的定量，TGFβmRNA的分析 周围单核细胞中的合成，评估关系 在燃烧血清的免疫抑制特性和TGFβ之间 活动，检查IL-6诱导TGF增加的能力 Beta和TGFβ受体表达在外周血上的研究 单核细胞。 最后，我们将研究TGF的可能机制 Beta通过针对的主要研究抑制淋巴细胞增殖 评估TGFβ对已知的主要基因的影响 参与淋巴细胞增殖反应。