Reciprocal Regulation of Cyclooxygenase 2 and Heme Oxygenase 1 upon Arsenic Trioxide Exposure in Normal Human Lung Fibroblast

Detoxification enzyme heme oxygenase 1 (HO-1) and proinflammation enzyme cyclooxygenase 2 (Cox-2) are key response proteins that function to promote the survival of cells exposed to arsenic trioxide (ATO). However, whether there is a cross-regulation between them in ATO-treated cells remains poorly investigated. In this study, concomitant upregulation of Cox-2 and HO-1 induced by ATO was observed in normal human lung fibroblasts. Cox-2 inhibitor NS398 suppressed the upregulation of HO-1, whereas HO-1 inhibitor protoporphyrin IX zinc (II) stimulated the expression of Cox-2. Both proteins were regulated by p38, and the feedback regulation of HO-1 on Cox-2 was mediated through p38. Our results confirmed the reciprocal regulations between Cox-2 and HO-1 in ATO-treated normal cells and shed light on the understanding of protecting cells from injury caused by ATO while simultaneously decreasing the inflammation responses, which may be related to the carcinogenicity of ATO. (c) 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:323-329, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.21491