Docosahexaenoic acid modulates in vitro the inflammation of celiac disease in intestinal epithelial cells via the inhibition of cPLA2.

Summary: Background & aims: The cytosolic phospolypase A₂ (cPLA₂) - dependent release of arachidonic acid (AA) from the intra-epithelial lymphocytes plays a pivotal role in arming lymphocytes to cytolysis in the immune response of celiac disease. However, little is known about the role of enterocytes in releasing AA. Docosahexaenoic acid (DHA) is a long chain polyunsaturated fatty acid that counteracts many of the proinflammatory effect of AA. The aims of the present work were to evaluate if: 1) intestinal epithelial cells have a role in the celiac inflammation, releasing AA, and 2) if DHA is able to modulate the celiac inflammation, down-regulating the release of AA. Methods: A human intestinal epithelial cell line (Caco-2) was exposed to gliadin peptides (PT-gl) (500 μg/ml) and DHA (2 μg/ml), both alone and simultaneously up to 24 h. Results: The exposure of those cells to PT-gl alone resulted in an increased AA release, cycloxygenase-2 expression, cPLA₂ activity and prostaglandin E₂ and interleukin-8 release in culture medium, whereas the simultaneous exposure of the cells to DHA and PT-gl prevented the above-mentioned increases. Conclusions: These results suggest that intestinal epithelial cells sustain the celiac inflammation, releasing AA when stimulated with gliadin and that DHA inhibits the AA release by these cells. [Copyright &y& Elsevier]