The Effect of Lipopolysaccharide on Noxa Expression Is Mediated through IRF1, 3, and 7.

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.