Nicotinamide Adenine Dinucleotide Phosphate Oxidase Expression Is Differentially Regulated to Favor a Pro-oxidant State That Contributes to Postoperative Adhesion Development

Abstract

We have previously reported that superoxide (O2•-) contributes to the development of postoperative adhesions. In this study, we determined whether O2•- generating nicotinamide adenine dinucleotide phosphate oxidase (NOX) is differentially expressed in normal peritoneal and adhesion fibroblasts and tissues. The NOX isoforms were measured utilizing Western blot, immunohistochemistry, high-performance liquid chromatography, and real-time reverse transcription polymerase chain reaction. Expression and activity of NOX were found to be significantly higher in adhesion tissues and cells than that in normal peritoneal tissues and cells (P < .05). Levels of NOX2, NOX4, NOX activating protein 1, DUOX1, p47phox, and p22phox messenger RNA increased in adhesion fibroblasts when compared to normal peritoneal and increased in response to hypoxia in normal peritoneal fibroblasts. Thus, adhesion fibroblasts are characterized by a unique NOX expression profile, which maintains a pro-oxidant state that may be responsible for the persistence of the adhesion phenotype. Decreasing the activity of NOX by targeting these isoforms may be beneficial for future therapeutic interventions of postoperative adhesions.