Regulation of class III major histocompatibility complex gene products by interleukin-1.

Regulation of class III major histocompatibility complex gene products by interleukin-1.
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IL-1 对 III 类主要组织相容性复合体基因产物的调节。

DOI:
10.1126/science.3010455
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发表时间:
1986
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Colten,HR
Colten,HR
中科院分区:
--
文献类型:
--
作者:
Perlmutter,DH;Goldberger,G;Dinarello,CA;Mizel,SB;Colten,HR

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白细胞介素-1 (IL-1)是单核吞噬细胞的产物,介导炎症或组织损伤反应(急性期反应)的特征变化。两个结构和功能同源的主要组织相容性复合体(MHC) III类基因之一编码阳性的急性期蛋白补体因子b,紧密相连的补体C2基因在急性期反应中不受影响。纯化的人IL-1 (pH 7.0)和重组生成的小鼠IL-1 (pH 5.0)增加了人肝癌细胞中因子B和其他阳性急性期蛋白的表达,但降低了白蛋白(一种阴性急性期反应物)的表达。此外,在转染了含有人类C2和因子B基因的cosmid DNA的小鼠成纤维细胞l细胞系中,IL-1介导了转染细胞中因子B表达的可逆剂量和时间依赖性增加。IL-1不影响C2基因的表达。IL-1对因子B表达的影响涉及翻译前水平的作用机制,具体表现为特异性信使RNA含量的增加和相应的因子B的生物合成和分泌的增加。这些基因选择性和独立调节的结构基础和机制为了解炎症反应的分子控制提供了新的视角。
Interleukin-1 (IL-1) is a product of mononuclear phagocytes that mediates changes characteristic of the response to inflammation or tissue injury (the acute-phase response). One of two structurally and functionally homologous major histocompatibility complex (MHC) class III genes encodes a positive acute-phase protein, complement factor B. The closely linked complement C2 gene is not affected during the acute-phase response. Purified human IL-1,pH 7.0, and recombinant-generated murine IL-1,pH 5.0, increased the expression of factor B and other positive acute-phase proteins in human hepatoma cells but decreased the expression of albumin, a negative acute-phase reactant. Furthermore, in a murine fibroblast L-cell line transfected with cosmid DNA bearing the human C2 and factor B genes, IL-1 mediated a reversible dose- and time-dependent increase in factor B expression in the transfected cells. Expression of the C2 gene was not affected by IL-1. The effect of IL-1 on factor B expression involves a mechanism acting at a pre-translational level as demonstrated by an increase in specific messenger RNA content and a corresponding increase in biosynthesis and secretion of factor B. The structural basis and mechanism for selective and independent regulation of these genes provides insight into the molecular control of the inflammatory response.