MODULATION OF T CELL ACTIVITY BY 2-ARACHIDONYL GLYCEROL

2-花生四烯酰甘油对 T 细胞活性的调节

• 批准号: 6718435
• 负责人: Cheryl Elizabeth Rockwell
• 金额: $ 2.71万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-16 至 2005-03-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6718435
• 关键词: T lymphocyte; cannabinoids; cell growth regulation; clone cells; cyclin dependent kinase; densitometry; enzyme inhibitors; enzyme linked immunosorbent assay; glycerol; human tissue; immunoregulation; immunosuppression; inhibitor /antagonist; interleukin 2; laboratory mouse; leukocyte activation /transformation; mitogen activated protein kinase; polymerase chain reaction; receptor expression; scintillation counter; spectrometry; western blottings

DESCRIPTION: (Provided by Applicant): Previous studies in this laboratory have demonstrated a marked and concentration-dependent inhibition of IL-2 by a putative endogenous cannabinoid, 2-arachidonyl glycerol (2-AG), in activated T cells, but it is yet unknown whether this inhibition is mediated through the cannabinoid receptors, CB1 and/or CB2. The CB2 receptor is of particular interest because it has a much higher level of expression than the CB1 receptor. The majority of our observations have thus far been in murine T cells. We are now interested in characterizing the effect of 2-AG in two human T cell lines, Jurkat E6-1 and HPB-ALL, which express an aberrant and normal CB2 receptor, respectively. The Jurkat and HPB-ALL cell lines in conjunction with the CB2 antagonist, SR144528, will allow us to determine if the activity of 2-AG in human T cells is mediated through the CB2 receptor. Preliminary studies led to the following observations: a) the inhibition of IL2 by 2-AG was not reversed by CB1/CB2 antagonists; b) 2-AG inhibited IL-2 transcription in HPB-ALL cells, but not in Jurkat cells, which express an aberrant CB2 receptor; and c) paradoxically, 2-AG also enhances T cell proliferation. These observations led to the hypothesis: 2-arachidonyl glycerol enhances T cell proliferation in a CB1/CB2 independent mechanism through alterations in cell cycle control and/or ERK MAP kinases, while inhibiting IL-2 production. This hypothesis will be tested using three specific aims (SA): SA1) characterization of the effects of 2-AG upon IL-2 transcription and secretion in human T cells; SA2) characterization on the effects of 2-AG upon T cell proliferation in human T cells; and SA3) characterization of the effects of 2-AG on the cyclin dependent kinase inhibitors, p16, p21, and p27, and the mitogen-activated kinases, ERK1 and ERK2.

描述：（由申请人提供）：