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अमूर्त

Paraoxonase Gene Expression in Pediatric Inflammatory Bowel Disease

Razan H Alkhouri, Susan S Baker, Humaira Hashmi, Wensheng Liu, Robert D Baker and Lixin Zhu

Background: Oxidative stress plays a role in the pathogenesis of inflammatory bowel disease (IBD). The Paraoxonase (PON) genes, expressed in the human intestine, are thought to prevent oxidative stress and modulate inflammation. We investigated the effect of IBD and steroids on PON gene. We hypothesized that PON gene expression is decreased in IBD patients and that steroid treatment would return it to normal.
Methods: Pediatric patients diagnosed with IBD, were enrolled and matched to control subjects. For in vitro studies, human epithelial colorectal adenocarcinoma (Caco-2) cells were treated with hydrogen peroxide (H₂O₂) and dexamethasone. PON genes expression was evaluated by quantitative real-time PCR for both the biopsies and the Caco-2 cells.
Results: PON gene expression was decreased in intestinal biopsies from medication naïve IBD patients when compared to controls (p<0.05). Biopsies from IBD patients on steroids exhibited up regulation of PON gene expression (p<0.05). Caco-2 cells treated with H₂O₂ had decreased PON gene expression compared to controls (p<0.05). Dexamethasone increased PON gene expression in Caco-2 cells (p<0.05).
Conclusion: Our data suggests that decreased PON expression in IBD patients is a consequence of oxidative stress which plays a role in the pathogenesis of IBD. Further, steroids counteract the effect of oxidative stress by up regulating PON gene expression. PON genes may be targets for the management of intestinal diseases like IBD.