Inflammatory reaction without endogenous antioxidant response in Caco-2 cells exposed to iron/ascorbate-mediated lipid peroxidation.
To characterize the role of intestinal epithelial cells in mucosal host defense, we have examined endogenous antioxidant reactivity and inflammatory response in Caco-2 cell line. When differentiated Caco-2 cells were incubated with iron/ascorbate for 1-24 h, they exhibited increased malondialdehyde levels and decreased polyunsaturated fatty acid proportion in favor of saturated fatty acids. These modifications were accompanied with alterations in membrane fluidity and permeability. The oxidative stress did not induce changes in the antioxidant enzyme activity of superoxide dismutase, catalase, glutathione peroxidase, and glutathione transferase, or in cellular glutathione content. However, iron/ascorbate-mediated lipid peroxidation promoted inhibitor-kappaB degradation and NF-kappaB activation, as well as gave rise to IL-8, cyclooxygenase-2, and ICAM-1. These results support the importance of oxidant/antioxidant balance in the epithelial cell inflammatory response.
Bernotti
Sandra
S
Centre de Recherche, Hôpital Sainte-Justine, 3175 Côte Ste-Catherine, Montreal, QC, Canada, H3T 1C5.
Seidman
Ernest
E
Sinnett
Daniel
D
Brunet
Sylvain
S
Dionne
Serge
S
Delvin
Edgard
E
Levy
Emile
E
D001205:Ascorbic Acid / Q000494:pharmacology*; D018938:Caco-2 Cells; D051546:Cyclooxygenase 2; D017097:Electric Impedance; D005227:Fatty Acids / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000209:etiology* / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007501:Iron / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D015227:Lipid Peroxidation; D008315:Malondialdehyde / Q000378:metabolism; D008560:Membrane Fluidity / Q000187:drug effects; D008565:Membrane Proteins; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D005227:Fatty Acids; D016166:Free Radical Scavengers; D020672:I-kappa B Proteins; D016209:Interleukin-8; D007527:Isoenzymes; D008565:Membrane Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; D008315:Malondialdehyde; D007501:Iron; D010088:Oxidoreductases; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D001205:Ascorbic Acid