Specialized pro-resolvin mediators induce cell growth and improve wound repair in intestinal epithelial Caco-2 cell cultures

Abstract

Specialized pro-resolvin mediators (SPMs) are a superfamily of bioactive molecules synthesized from polyunsaturated fatty acids (arachidonic, eicosapentaenoic and docosahexaenoic acids) that include resolvins, protectins and maresins. These metabolites are important to control the resolution phase of inflammation and the epithelial repair, which is essential in restoring the mucosal barriers. Unfortunately, the effects of SPMs on intestinal epithelial cell growth remain poorly understood. Caco-2 cell were used as intestinal epithelial cell model. Cell growth/DNA synthesis, cell signalling pathways, western blot and wound repair assay were performed. Our data demonstrated that SPMs such as lipoxin LxA₄, resolvin (Rv) E1, RvD1, protectin D 1 and maresin 1 were able to enhance intestinal epithelial Caco-2 cell growth and DNA synthesis. Furthermore, our results provide evidence that these effects of RvE1 and RvD1 were associated with a pertussis toxin-sensitive G protein-coupled receptor, and that leukotriene B₄ receptor 2 could be involved, at least in part, in these effects of RvE1/RvD1. Moreover, these mitogenic effects induced by SPMs were dependent on the ERK 1/2 and p38 MAPK pathways as well as phospholipase C and protein kinase C activation. Thus, these mitogenic effects of RvE1/RvD1 on intestinal epithelial cells could be involved in this signalling circuit involved in wounded epithelium and the catabasis process.