Zhang J S, Feng W G, Li C L, Wang X Y, Chang Z L
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
Cell Immunol. 2000 Aug 25;204(1):38-45. doi: 10.1006/cimm.2000.1690.
NF-kappa B plays a critical role in coordinating the control of gene expression during monocyte/macrophage activation. In this report we describe our investigation of the mechanisms of LPS-induced NF-kappa B activation and IL-12 expression in murine peritoneal suppressor macrophages. Treatment of these macrophages with LPS induced I kappa B alpha degradation and NF-kappa B activation. EMSAs demonstrated that NF-kappa B bound to a cis-acting element located in the murine IL-12 p40 promoter. LPS signal transduction has been shown to involve a variety of signal pathways. The results in this paper indicate that LPS-induced NF-kappa B binding activity was independent of PKC, PKA, ERK, and p38 MAPK, but was regulated by proteasome. Furthermore, Proteasome Inhibitor I abolished the LPS-induced mRNA expression of IL-12 p35 and p40, and SB203580 reduced these mRNA levels, whereas the blockade of PKC, PKA, and ERK had little effect. These data demonstrate that the LPS-induced activation of proteasome. I kappa B. NF-kappa B and p38 MAPK signal pathways regulate the IL-12 expression in murine peritoneal suppressor macrophages.
核因子-κB在单核细胞/巨噬细胞激活过程中协调基因表达调控方面发挥着关键作用。在本报告中，我们描述了对小鼠腹腔抑制性巨噬细胞中脂多糖（LPS）诱导的核因子-κB激活及白细胞介素-12（IL-12）表达机制的研究。用LPS处理这些巨噬细胞可诱导IκBα降解及核因子-κB激活。电泳迁移率变动分析（EMSA）表明，核因子-κB与位于小鼠IL-12 p40启动子中的顺式作用元件结合。已证明LPS信号转导涉及多种信号通路。本文结果表明，LPS诱导的核因子-κB结合活性独立于蛋白激酶C（PKC）、蛋白激酶A（PKA）、细胞外信号调节激酶（ERK）和p38丝裂原活化蛋白激酶（p38 MAPK），但受蛋白酶体调节。此外，蛋白酶体抑制剂I消除了LPS诱导的IL-12 p35和p40的mRNA表达，SB203580降低了这些mRNA水平，而阻断PKC、PKA和ERK的作用甚微。这些数据表明，LPS诱导蛋白酶体、IκB、核因子-κB和p-38 MAPK信号通路的激活，从而调节小鼠腹腔抑制性巨噬细胞中IL-12的表达。
