Abstract 3487: Molecular basis for induction of IL-8 expression by thymidine phosphorylase

Abstract

Abstract Thymidine phosphorylase (TP) is identical to platelet-derived endothelial cell growth factor (PD-ECGF) and has an angiogenic activity. 2-Deoxy-D-ribose, one of the degradation products of thymidine, is a down stream mediator of the TP function. We investigated the molecular basis for the induction of an angiogenic factor, interleukin-8 (IL-8) by TP. First we confirmed that the enzymatic activity of TP is needed for the induction of IL-8 by TP in KB cells, and 2-deoxy-D-ribose increased the expression level of IL-8. ROS generated by TP augmented the expression of heme oxygenase-1 (HO-1) and increased the expression of IL-8. Two inhibitors of NADPH oxidase, apocynin and diphenyleneiodonium, suppressed the expression of HO-1 and IL-8 in TP-overexpressing KB/TP cells. Knock down of the component of NADPH oxidase, Nox2 or p22phox, also suppressed the enhanced expression of IL-8 in KB/TP cells. ROS generated by TP activated NFκB, which subsequently enhanced the promoter activity of IL-8. Our findings suggest that NADPH oxidase is involved in the ROS generation by TP, and the ROS caused the activation of NF-κB, which subsequently enhanced the expression of IL-8. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3487. doi:10.1158/1538-7445.AM2011-3487