Piya Sujan, Kim Tae-Hyoung
Department of Biochemistry, Chosun University School of Medicine, Gwangju 61452, Republic of Korea.
J Microbiol Biotechnol. 2018 Mar 28;28(3):491-497. doi: 10.4014/jmb.1708.08054.
Lipopolysaccharide (LPS), a component of the cell wall of gram-negative bacteria, elicits the secretion of cytokines, such as interferons, that stimulate the host defense system. Previously, we demonstrated that interferons induce interferon regulatory factors (IRFs) 1, 3, and 7, which regulate the transcription of Noxa and alter the expression profiles of Bcl-2 family proteins in tumors. However, the immediate consequences of LPS stimulation on Noxa and BH3 expression in tumor cells remain uncharacterized. In this study, we determined that LPS induced Noxa expression in CT26 cells. Furthermore, studies in HCT116 parental and HCT116 p53-deficient cells revealed that LPS-mediated Noxa was independent of p53. Meanwhile, IRF1, 3, and 7 in CT26, HCT116 parental, and HT116 p53-deficient cells were upregulated by LPS stimulation, suggesting that LPS induces the expression of these IRFs in a p53-independent manner. The responsiveness of IRF1, 3, 4, and 7 binding to the Noxa promoter region to LPS indicated that IRF1, 3, and 7 activated Noxa expression, whereas IRF4 repressed Noxa expression. Together, these results suggest that LPS directly affects Noxa expression in tumor cells through IRFs, implicating that it may contribute to LPS-induced tumor regression.
脂多糖（LPS）是革兰氏阴性菌细胞壁的一种成分，可引发细胞因子的分泌，如干扰素，从而刺激宿主防御系统。此前，我们证明干扰素可诱导干扰素调节因子（IRF）1、3和7，这些因子可调节Noxa的转录并改变肿瘤中Bcl-2家族蛋白的表达谱。然而，LPS刺激对肿瘤细胞中Noxa和BH3表达的直接影响仍未明确。在本研究中，我们确定LPS可诱导CT26细胞中Noxa的表达。此外，对HCT116亲本细胞和HCT116 p53缺陷细胞的研究表明，LPS介导的Noxa与p53无关。同时，LPS刺激可上调CT26、HCT116亲本细胞和HT116 p53缺陷细胞中的IRF1、3和7，这表明LPS以p53非依赖的方式诱导这些IRF的表达。IRF1、3、4和7与Noxa启动子区域结合对LPS的反应表明，IRF1、3和7激活Noxa表达，而IRF4抑制Noxa表达。总之，这些结果表明LPS通过IRF直接影响肿瘤细胞中Noxa的表达，这意味着它可能有助于LPS诱导的肿瘤消退。
