Control of LMP7 expression in human endothelial cells by cytokines regulating cellular and humoral immunity

Control of LMP7 expression in human endothelial cells by cytokines regulating cellular and humoral immunity
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DOI:
10.1006/cyto.2000.0717
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发表时间:
2000-09-01
期刊:
影响因子:
3.8
通讯作者:
Nelson, JE
Nelson, JE
中科院分区:
医学3区
文献类型:
--
作者:
Loukissa, A;Cardozo, C;Nelson, JE

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多催化蛋白酶复合物(MPC、蛋白酶体)通过掺入可由 IFN-γ 和 TNF-α 诱导的三个亚基(LMP2、LMP7 和 LMP10),促进抗原肽的形成。这些细胞因子或其功能同源物(例如 TNF-β)由许多细胞(包括 Th-1 淋巴细胞)释放。为了更多地了解细胞免疫的控制与 LMP 亚基表达之间的关系,我们测量了促进细胞免疫(IL-12、IFN-γ、TNF-α)或体液免疫(IL-10、IL-6)的细胞因子的人脐静脉内皮细胞中的 LMP7 水平。当细胞单独暴露于 IL-6、IL-10 或 IL-12 时,几乎没有看到任何影响。 IFN-γ 上调 LMP7 水平,TNF-α 也上调 LMP7 水平,但程度较小。 IL-10 下调 IFN-γ 诱导的 LMP7 水平升高,IL-12 也是如此。研究结果表明,LMP7 水平的调节与 MHC I 类依赖性免疫所需的其他分子的调节类似,并且可能与其相关,并且主要取决于 Th-1 辅助淋巴细胞释放的细胞因子。 (C) 2000 年学术出版社。
Formation of antigenic peptides by the multicatalytic proteinase complex (MPC, proteasome) is facilitated by incorporation of three subunits (LMP2, LMP7 and LMP10) that are inducible by IFN-gamma and TNF-alpha. These cytokines, or their functional homologues (e.g. TNF-beta), are released from many cells including Th-1 lymphocytes. To learn more about the relationship between control of cellular immunity and expression of LMP subunits, we measured LMP7 levels in human umbilical vein endothelial cells of cytokines promoting cellular immunity (IL-12, IFN-gamma, TNF-alpha) or humoral immunity (IL-10, IL-6). Little or no effect was seen when cells were exposed to IL-6, IL-10 or IL-12 alone. IFN-gamma upregulated LMP7 levels, as did TNF-alpha to a lesser extent. IL-10 downregulated IFN-gamma-induced increases in LMP7 levels, as did IL-12. The findings indicate that regulation of levels of LMP7 is similar to and may be coupled with that of other molecules required for MHC class I-dependent immunity, and depends primarily on cytokines released by Th-1 helper lymphocytes. (C) 2000 Academic Press.