IL-18 enhances thrombospondin-1 production in human gastric cancer via JNK pathway
IL-18 enhances thrombospondin-1 production in human gastric cancer via JNK pathway
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DOI：
10.1016/j.bbrc.2006.04.016
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发表时间：
2006-06-16
影响因子：
3.1
通讯作者：
Cho, Daeho
中科院分区：
文献类型：
--
作者：
Kim, Jihye;Kim, Cherlhyun;Cho, Daeho
IL-18是由许多癌细胞产生的多效性细胞因子。最近的报告表明，IL-18在调节黑色素瘤和胃癌细胞的免疫逃逸中起关键作用。血小板反应蛋白（TSP-1）是已知的抑制血管生成在几种癌症，但一些研究报告，它刺激血管生成在一些癌症，如胃癌。IL-18和TSP-1与肿瘤的增殖和转移有关。本研究旨在探讨IL-18和TSP-1在胃癌中的关系。RT-PCR和ELISA结果显示，IL-18处理后，细胞TSP-1 mRNA表达和TSP-1蛋白产生水平均呈剂量和时间依赖性增加。接下来用特异性抑制剂处理细胞，以确定参与IL-18增强的TSP-1产生的信号通路。IL-18增强的TSP-1表达被c-Jun N-末端激酶（JNK）特异性抑制剂SP 600125阻断。Western blot结果显示，IL-18可促进磷酸化JNK的表达。总之，这些结果表明IL-18在涉及JNK的TSP-1表达中起关键作用。(c)2006年爱思唯尔公司All rights reserved.
IL-18 is a pleiotropic cytokine that is produced by many cancer cells. A recent report suggested that IL-18 plays a key role in regulating the immune escape of melanoma and gastric cancer cells. Thrombospondin (TSP-1) is known to inhibit angiogenesis in several cancers but some studies have reported that it stimulates angiogenesis in some cancers such as gastric cancer. IL-18 and TSP-1 are related to tumor proliferation and metastasis. This study investigated the relationship between IL-18 and TSP-1 in gastric cancer. RT-PCR and ELISA showed that after the cells had been treated with IL-18, the level of TSP-1 mRNA expression and TSP-1 protein production by IL-18 increased in both a dose- and time-dependent manner. The cells were next treated with specific inhibitors in order to determine the signal pathway involved in IL-18-enhanced TSP-1 production. IL-18-enhanced TSP-1 expression was blocked by SP600125, a c-Jun N-terminal kinase (JNK) specific inhibitor. In addition, Western blot showed that IL-18 enhanced the expression of phosphorylated JNK. Overall, these results suggest that IL-18 plays a key role in TSP-1 expression involving JNK. (c) 2006 Elsevier Inc. All rights reserved.