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A more recent version of this article appeared on July 1, 2006

Papers In Press, published online ahead of print April 3, 2006
J. Lipid Res., doi:10.1194/jlr.M500564-JLR200
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Submitted on December 27, 2005
Revised on March 28, 2006
Accepted on April 2, 2006

Arachidonic acid cascade and epithelial barrier function during Caco-2 cell differentiation

Raquel Martín-Venegas, Sònia Roig-Pérez, Ruth Ferrer, and Juan Jose Moreno

Physiology, University of Barcelona, Barcelona E-08028

Corresponding Author: jjmoreno{at}ub.edu

The small intestinal epithelium is a highly dynamic system continuously renewed by a process involving cell proliferation and differentiation. The intestinal epithelium constitutes a permeability barrier regulating the vectorial transport of ions, water and solutes. Morphological changes during cell differentiation, as well as changes in the activity of brush-border enzymes and the expression of transport proteins, have been well established. However, little remains known about the arachidonic acid cascade underlying epithelial cell differentiation or its role in the development of epithelial barrier function. The main purpose of this study was to examine the activity of high-molecular phospholipases A2 and cyclooxygenase pathway during differentiation, with particular emphasis on paracellular permeability. Phospholipase A2 activity, arachidonic acid release, cyclooxygenase-2 expression, prostaglandin E2 production, and paracellular permeability were studied in preconfluent, confluent, and differentiated Caco-2 cell cultures. Our results show that Caco-2 differentiation induces a decrease in both calcium-independent phospholipase A2 activity and cyclooxygenase-2 expression, and consequently, a decrease in arachidonic acid release and prostaglandin E2 synthesis in parallel with a reduction in paracellular permeability. Moreover, the addition of prostaglandin E2 to differentiated cells, at concentrations similar to those detected in non-differentiated cultures, induces the disruption of the epithelial barrier function. These results suggest that arachidonic acid release by calcium-independent phospholipase A2, cyclooxygenase-2 expression and subsequent prostaglandin E2 release are important for the maintenance of paracellular permeability in differentiated Caco-2 cells.


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