BONE-SEEKING HORMONES AND THE IMMUNE SYSTEM

该项目旨在探索1，25 （OH）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都是 靶向免疫细胞的有效骨吸收剂，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非转化的辅助性T细胞系。 至于1，25（OH）2D对T细胞增殖的影响，我们 已经表明，类固醇是一个强大的有丝分裂原的克隆下， 研究，具体目标#1是针对探索细胞 这种增殖现象背后的机制。 这些 研究将集中在类固醇诱导或 增加已知可增强T细胞增殖的生长因子的表达 淋巴细胞生长（例如，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侧重于手段， IL-1刺激T细胞增殖。 尽管IL-1已知 作为一种关键的T细胞生长因子，其促有丝分裂作用 通常需要共刺激物如特异性抗原或凝集素。 由于难以区分IL-1介导的对 淋巴细胞从thos的一个共同的有丝分裂原，手段，IL-1 促进T细胞复制是未知的。 或者，我们有 开发了另一种对IL-1有独特反应的T细胞系 单独使用而不需要促分裂原，将我们置于 位置，以探索这种生长因子的确切影响， 淋巴细胞 这些实验将集中在IL-1的能力， 1以立即改变细胞蛋白质 磷酸化，并将探讨可能参与 蛋白激酶C或酪氨酸激酶在IL-1介导 方面的影响.

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.