出版社：American Society for Biochemistry and Molecular Biology
摘要：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, are well established. However, little is known about the arachidonic acid (AA) 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 the high-molecular-weight phospholipases A2 (PLA2) and cyclooxygenase (COX) pathway during differentiation, with particular emphasis on paracellular permeability. PLA2 activity, AA release, COX-2 expression, prostaglandin E2 (PGE2) 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 PLA2 activity and COX-2 expression and, consequently, a decrease in AA release and PGE2 synthesis in parallel with a reduction in paracellular permeability. Moreover, the addition of PGE2 to differentiated cells, at concentrations similar to those detected in nondifferentiated cultures, induces the disruption of epithelial barrier function. These results suggest that AA release by calcium-independent PLA2, COX-2 expression, and subsequent PGE2 release are important for the maintenance of paracellular permeability in differentiated Caco-2 cells.
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