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Intestinal paraoxonase regulation and its status in Crohn’s disease
Author(s) -
Precourt LouisPhilippe,
Delvin Edgard,
Amre Devendra,
Sinnett Daniel,
Seidman Ernest,
Levy Emile
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1321
Subject(s) - pon1 , paraoxonase , oxidative stress , lipopolysaccharide , crohn's disease , lipoprotein , medicine , pathogenesis , reactive oxygen species , secretion , endocrinology , inflammatory bowel disease , immunology , inflammation , chemistry , disease , cholesterol , biology , biochemistry , gene , genotype
The current paradigm on the pathogenesis of Crohn’s disease (CD) focuses on the excessive secretion of numerous inflammatory mediators by the dense inflammatory cell infiltrates in response to luminal bacterial products such as lipopolysaccharide (LPS). Various studies have provided evidence of an important role of oxidant injury in intestinal epithelial cells. The objectives of the present investigation are to test the hypotheses that (i) the concentration and composition of high‐density lipoprotein (HDL) is altered in CD; (ii) as a consequence, paraoxonase (PON) contained in HDL may be reduced; and (iii) the gene expression of PON1, PON2 and PON3 in the intestine are modulated by lipid peroxides, inflammatory cytokines and LPS. Our results document that, concomitant with the occurrence of oxidative stress, marked abnormalities are observed in the chemical composition and concentration of HDL 2 and HDL 3 of patients with CD. Furthermore, the protein content of PON1 is decreased in HDL fractions. Finally, the transcripts of PON1, PON2 and PON3 in cultured Caco‐2 cells are distinctly modulated by iron‐ascorbate oxygen‐radical generating system, LPS, interferon‐γ and TNFα. For example, interferon‐γ decreased PON1, raised PON2 and remained without effect on PON3. Our data support the notion that paraoxonases are key factors involved in intestinal mucosal and peripheral defense against oxidative stress in CD. This study is supported by Crohn’s and Colitis Foundation of Canada.