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Am J Physiol Gastrointest Liver Physiol (July 3, 2003). doi:10.1152/ajpgi.00042.2003
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Submitted on January 24, 2003
Accepted on June 20, 2003

INFLAMMATORY REACTION WITHOUT ENDOGENOUS ANTIOXIDANT RESPONSE IN CACO-2 CELLS EXPOSED TO IRON / ASCORBATE-MEDIATED LIPID PEROXIDATION

Sandra Bernotti1, Ernest Seidman2, Daniel Sinnett3, Sylvain Brunet1, Serge Dionne4, Edgard Delvin5, and Emile Levy1*

1 Centre de Recherche, Hopital Sainte-Justine, Montreal, Quebec, Canada; Department of Nutrition, Universite de Montreal, Montreal, Quebec, Canada
2 Centre de Recherche, Hopital Sainte-Justine, Montreal, Quebec, Canada; Department of Pediatrics, Universite de Montreal, Montreal, Quebec, Canada
3 Centre de Recherche, Hopital Sainte-Justine, Montreal, Quebec, Canada; Department of Pediatrics, Universite de Montreal, Montreal, Quebec, Canada; Department of Biochemistry, Universite de Montreal, Montreal, Quebec, Canada
4 Centre de Recherche, Hopital Sainte-Justine, Montreal, Quebec, Canada
5 Centre de Recherche, Hopital Sainte-Justine, Montreal, Quebec, Canada; Department of Biochemistry, Universite de Montreal, Montreal, Quebec, Canada

* To whom correspondence should be addressed. E-mail: levye{at}justine.umontreal.ca.

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 1-24h, they exhibited increased MDA 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 I{kappa}B degradation and NF-{kappa}B activation, as well as gave rise to interleukin-8, COX-2 and ICAM-1. These results support the importance of oxidant/antioxidant balance in the epithelial cell inflammatory response.




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