Sulindac, a nonsteroidal anti-inflammatory drug, selectively inhibits interferon-γ-induced expression of the chemokine CXCL9 gene in mouse macrophages
Sulindac, a nonsteroidal anti-inflammatory drug, selectively inhibits interferon-γ-induced expression of the chemokine CXCL9 gene in mouse macrophages
复制标题
DOI：
10.1016/j.bbrc.2006.09.058
复制
发表时间：
2006-11-17
影响因子：
3.1
通讯作者：
Ohmori, Yoshihiro
中科院分区：
文献类型：
--
作者：
Sakaeda, Yoshiichi;Hiroi, Miki;Ohmori, Yoshihiro
舒林酸是一种非甾体抗炎药，已被证明对几种类型的癌症具有抗肿瘤作用。为了确定舒林酸对宿主免疫细胞（如巨噬细胞）细胞内信号传导途径的影响，我们研究了药物对干扰素γ（IFN γ）诱导的小鼠巨噬细胞样细胞系RAW 264.7细胞中信号转导和转录激活因子I（STATI）和其他基因表达的影响。舒林酸，而不是阿司匹林或水杨酸钠，抑制IFN γ诱导的CXC配体9（CXCL 9）mRNA的表达，CXCL 9是活化T细胞的趋化因子，而干扰素诱导的CXCL 1 O或IFN调节因子-1的表达不受舒林酸的影响。荧光素酶报告基因分析表明，舒林酸抑制IFN γ诱导的CXCL 9基因启动子活性。令人惊讶的是，舒林酸对IFN γ诱导的STATI活化没有抑制作用;然而，组成性核因子κ B活性被药物抑制。这些结果表明，舒林酸选择性抑制IFN γ诱导的基因表达，而不抑制STATI激活。(c)2006年爱思唯尔公司All rights reserved.
Sulindac, a non-steroidal anti-inflammatory drug, has been shown to exert an anti-tumor effect on several types of cancer. To determine the effect of sulindac on intracellular signaling pathways in host immune cells such as macrophages, we investigated the effect of the drug on interferon gamma (IFN gamma)-induced expression of signal transducer and activator of transcription I (STATI) and other genes in mouse macrophage-like cell line RAW264.7 cells. Sulindac, but not aspirin or sodium salicylate, inhibited IFN gamma-induced expression of the CXC ligand 9 (CXCL9) mRNA, a chemokine for activated T cells, whereas the interferon-induced expression of CXCL1O or IFN regulatory factor-1 was not affected by sulindac. Luciferase reporter assay demonstrated that sulindac inhibited IFN gamma-induced promoter activity of the CXCL9 gene. Surprisingly, sulindac had no inhibitory effect on IFN gamma-induced STATI activation; however, constitutive nuclear factor kappa B activity was suppressed by the drug. These results indicate that sulindac selectively inhibited IFN gamma-inducible gene expression without inhibiting STATI activation. (c) 2006 Elsevier Inc. All rights reserved.