Paraoxonases are associated with intestinal inflammatory diseases and intracellularly localized to the endoplasmic reticulum.
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.
Department of Gastroenterology, Meyer Children's Hospital, Rambam Health Care Campus, Haifa, Israel. l_rotem@rambam.health.gov.il
Lilah
L
Rothem
Corina
C
Hartman
Aviva
A
Dahan
Jesse
J
Lachter
Rami
R
Eliakim
Raanan
R
Shamir
D043303:Aryldialkylphosphatase / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D001706:Biopsy; D002446:Celiac Disease / Q000201:enzymology* / Q000235:genetics; D045744:Cell Line, Tumor; D003093:Colitis, Ulcerative / Q000201:enzymology* / Q000235:genetics; D003424:Crohn Disease / Q000201:enzymology* / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D004950:Esterases / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans
D004950:Esterases; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; C468411:PON2 protein, human; C113656:PON3 protein, human