Stress-activated protein kinase Jun N-terminal kinase is required for interleukin (IL)-1-induced IL-6 and IL-8 gene expression in the human epidermal carcinoma cell line KB
Stress-activated protein kinase Jun N-terminal kinase is required for interleukin (IL)-1-induced IL-6 and IL-8 gene expression in the human epidermal carcinoma cell line KB
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DOI：
10.1074/jbc.273.37.23681
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发表时间：
1998-09-11
影响因子：
4.8
通讯作者：
Kracht, M
中科院分区：
文献类型：
--
作者：
Krause, A;Holtmann, H;Kracht, M
细胞因子白细胞介素-1（IL-1）是一种主要的炎症激素，其在炎症期间激活广泛的基因。由IL-1触发的信号传导机制包括激活几种不同的蛋白激酶系统。应激激活蛋白激酶（SAPK），也称为Jun N-末端激酶（JNK），被细胞因子激活得特别强烈。在试图描述其在IL-1激活基因表达中的作用时，我们通过在人表皮癌细胞中稳定过表达SAPK β的无催化活性突变体（SAPK β（K-R））或SAPK β的反义RNA来抑制IL-1诱导的SAPK/JNK活性。在这些细胞中的信号转导的详细分析表明，激活NF κ B B，也没有p38丝裂原活化蛋白激酶的影响，这表明我们实现了特异性阻断SAPK/JNK。在未转染和载体转染的KB细胞中，IL-1诱导IL-6和IL-8 mRNA表达的强烈增加，沿着大量蛋白质的合成。在稳定过表达突变体SAPK β（K-R）的两个KB细胞克隆和稳定过表达SAPK β的反义RNA的三个克隆中，响应于IL-1的IL-6和IL-8的表达在mRNA和蛋白质水平上均强烈降低。这些数据表明，SAPK/JNK途径为IL-1诱导的IL-6和IL-8表达提供了不可或缺的信号。
The cytokine interleukin-l (IL-1) is a major inflammatory hormone which activates a broad range of genes during inflammation. The signaling mechanisms triggered by IL-1 include activation of several distinct protein kinase systems. The stress-activated protein kinase (SAPK), also termed Jun N-terminal kinase (JNK), is activated particularly strongly by the cytokine. In an attempt to delineate its role in activation of gene expression by IL-1, we inhibited the IL-l-induced SAPK/JNK activity by stable overexpression of either a catalytically inactive mutant of SAPK beta (SAPK beta(K-R)) or antisense RNA to SAPK beta in human epidermal carcinoma cells. A detailed analysis of signal transduction in those cells showed that activation of neither NF kappa B nor p38 mitogen-activated protein kinase was affected, suggesting that we achieved specific blockade of the SAPK/JNK. In untransfected and vector-transfected KB cells, IL-1 induced a strong increase in expression of IL-6 and IL-8 mRNA, along with the synthesis of high amounts of the proteins. In two KB cell clones stably overexpressing the mutant SAPK beta(K-R), and three clones stably overexpressing antisense RNA to SAPK beta, expression of IL-6 and IL-8 in response to IL-1 was strongly reduced at both the mRNA and protein level. These data indicate that the SAPK/JNK pathway provides an indispensable signal for IL-l-induced expression of IL-6 and IL-8.