BONE-SEEKING HORMONES AND THE IMMUNE SYSTEM

该项目旨在探索1，25 (2)2D和IL-1促进辅助性T淋巴细胞增殖。 这些问题与理解 骨质疏松症的发病机制：1)1，25(OH)2D和IL-1 以免疫细胞为靶点的强效骨吸收药，2) 免疫系统可能在调节 骨骼重塑，以及3)两种药物的异常产生 与骨质疏松症有关。 我们的研究将利用两个未转化的辅助性T细胞系。 关于1，25(OH)2D对T细胞增殖的影响，我们 已经证明类固醇是克隆人的有效有丝分裂原 研究，具体目标#1是针对探索细胞 这种扩散现象背后的机制。这些 研究将集中在类固醇诱导或 增加已知可增强T细胞的生长因子的表达 淋巴细胞生长(如IL-1、IL-2、BSF-1)和/或增加 它们各自的细胞膜受体的数量。 另一方面，具体目标#2侧重于通过 其中IL-1刺激T细胞增殖。尽管已知Il-1 作为一种关键的T细胞生长因子，其有丝分裂作用 通常需要共同刺激，如特定的抗原或凝集素。 由于很难区分IL-1对血管内皮细胞的影响 来自共有丝分裂原的淋巴细胞，IL-1通过这种方式 促进T细胞复制的作用尚不清楚。或者，我们有 开发出另一种对IL-1有独特反应的T细胞系 独自一人，不需要有丝分裂原，把我们放在 探索这一生长因子对 淋巴细胞。这些实验将集中在IL-1的能力上。 1使细胞蛋白质立即发生变化 并将探索可能参与的磷酸化 IL-1介导的蛋白激酶C或酪氨酸激酶 效果。

This project is aimed at exploring the mechanisms by which 1,25 (OH)2D and IL-1 promote helper T lymphocyte proliferation. These issues are particularly germane to understanding the pathogenesis of osteoporosis as 1) both 1,25 (OH)2D and IL-1 are potent bone resorbing agents which target to immune cells, 2) the immune system probably plays an important role in regulating skeletal remodeling, and 3) abnormal production of both agents has been associated with osteoporosis. Our studies will utilize two non-transformed helper T cell lines. As regards the effect of 1,25 (OH)2D on T cell proliferation, we have shown that the steroid is a potent mitogen of the clone under study, and Specific Aim #1 is directed at exploring the cellular mechanisms underlying this proliferative phenomenon. These studies will focus on the capacity of the steroid to induce or increase the expression of growth factors known to enhance T lymphocyte growth (e.g., IL-1, IL-2, BSF-1) and/or increase the number of their respective cell membrane receptors. Specific Aim #2, on the other hand, focuses on the means by which IL-1 stimulates T cell proliferation. Although Il-1 is known to be a pivotal T cell growth factor, its mitogenic effect generally requires a co-stimulus such as specific antigen or lectin. As it is difficult to distinguish IL-1 mediated effects on lymphocytes from thos of a co-mitogen, the means by which IL-1 promotes T cell replication are unknown. Alternatively, we have developed another T cell line which uniquely responds to IL-1 alone without the necessity of a co-mitogen, placing us in a position to explore the precise effects of this growth factor on lymphocytes. These experiments will focus on the capacity of IL- 1 to effect immediate alterations in cellular protein phosphorylation and will explore the possible involvement of either protein kinase C or tyrosine kinase in the IL-1 mediated effects.