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Paraoxonases are associated with intestinal inflammatory diseases and intracellularly localized to the endoplasmic
Lilah Rothem1, Corina Hartman, Aviva Dahan
1Department of Gastroenterology, Meyer Children's Hospital, Rambam Health Care Campus, Haifa, Israel. l_rotem@rambam.health.gov.il
Abstract:
We demonstrated previously that the paraoxonase (PON1/2/3) genes and proteins are expressed in human intestinal biopsies and in Caco-2 cells. The current study aims were to explore whether PON1/2/3 expression is different in inflammatory bowel diseases (IBD) or celiac disease compared to healthy controls, and to explore the intracellular localization of PON1/2/3. Our results showed that significantly fewer biopsies expressed PON1 and PON3 in the duodenum of celiac patients (PON1, P<0.0001; PON3, P=0.03), in the terminal ileum of Crohn's patients (PON1, P=0.001; PON3, P=0.008), and in the colon of UC patients (PON1, P=0.02; PON3, P=0.06) compared to controls. Since all three disorders share markedly elevated inflammatory mediators we explored the PON1/2/3 mRNA expression on cytokine stimulation. No changes were observed in Caco-2 and HT29 cells. Immunofluorescence experiments localized PON1/2/3 exclusively to the endoplasmic reticulum (ER) in both CaCo-2 and HT29 cells. These results demonstrate for the first time a novel relationship between PON1 and PON3 expression and several inflammatory gastrointestinal disorders. Together with the localization of PON1/2/3 enzymes to the ER, it may be suggested that PON1/2/3 may have extracellular functions as part of the host response in IBD and celiac disease.
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