It is now recognized that epithelial cells are critical cell population in the initiation, regulation and resolution of innate and adaptive immune responses at mucosal sites. Thus, the intestinal epithelium forms a regulated and selectively permeable barrier that allows passage of nutrients, but restricts the access of potential harmful substances. These events are consequence, at least in part, of a highly dynamic continuously renewed/repair processes involving cell proliferation and migration.

Arachidonic acid (AA), a common n−6 polyunsaturated fatty acid (PUFA), is found esterified at the sn-2 position of membrane phospholipids. When AA is released, it is oxidized by cyclooxygenases (COX) to produce prostaglandins (PG) such as PGE₂. Moreover, AA is also metabolized by lipoxygenases (LOX) producing leukotrienes (LT) such as LTB₄ and hydroxyeicosatetraenoic acids (HETEs). Eicosapentaenoic acid (EPA), an n–3 PUFA found mainly in fish oil, can also function as a substrate for COX-2 and LOXs resulting in the synthesis of 3-series PG, 5-series LT and hydroxyeicosapentaenoic acids (HEPEs)⁽Reference Needleman^1, Reference Kobayashi²⁾. Recently, we observed the role of AA metabolites produced by COX on Caco-2 cell growth⁽Reference Sánchez and Moreno^3, Reference Martín-Venegas⁴⁾. Moreover, AA metabolites of LOX pathway are also involved in epithelial cell proliferation⁽Reference Moreno⁵⁾. Taking into account the above-mentioned facts, we sought to investigate the effect of n–3 and n−6 eicosanoids on Caco-2 cell proliferation.

Cell growth was determined by microscopic assay using ethidium bromide/acridine orange staining in preconfluent Caco-2 cell cultures in the presence of eicosanoids (48 h). The data (n=6–9 for each condition) were compared by Student's t test and in all cases, *P<0.05 was considered to denote significance.

Our results show that PGE₂ and PGE₃ (0.1–10 nM) significantly induce Caco-2 growth in a concentration-dependent manner, reaching an enhancement of almost 100% respect to control condition (Fig. 1). Interestingly, the effect of PGE₃ was slight higher than PGE₂ and both were blocked by EP₁ (SC19220, 60 nM) and EP₄ (AH23848, 20 nM) antagonist, but not by EP₂ (ONO240, 2 nM) antagonist. LTB₄ (1–100 nM) was also able to significantly increase Caco-2 proliferation (50%), whereas LTB₅ was without effect (Figure 2). This mitogenic effect of LTB₄ (10 nM) was completely reverted by a BLT1 antagonist (U75032, 1 μM). Finally, we observed that 12-HETE and 12-HEPE (0.1 μM) present a significant proliferative action on intestinal epithelial cells (Fig. 3). Thus, n–3 and n−6 eicosanoids synthetised by COX-2 and 12-LOX might be involved in the control of renewed/repair processes in the intestinal epithelium, whereas n–3 but not n−6 metabolites from 5-LOX could also participate in these events.