Effect of arachidonic and eicosapentaenoic acid metabolism on RAW 264.7 macrophage proliferation.
Prostaglandins (PGs) and leukotrienes (LTs) derived from arachidonic acid (AA) are potent mediators of inflammation and cell proliferation. Dietary intake of eicosapentaenoic acid (EPA) appears beneficial to both inflammatory processes and cell proliferation. However, there is no clear mechanism explaining these effects. In this study, we investigated the effect of EPA on the AA incorporation in phospholipid membranes, on AA release and metabolism, and consequently, on PG synthesis. Our results showed not only that [(3)H]AA and [(14)C]EPA were similar incorporated into RAW 264.7 macrophage membranes, but also that the redistribution pattern between phospholipids was alike. [(3)H]AA or [(14)C]EPA release was induced by fetal bovine serum (FBS) in a similar fashion with AA metabolizing 3-fold more than EPA. In this way, we observed that AA could be metabolized by cyclooxygenase (COX)-1, COX-2 and 5-lipoxygenase (5-LOX) whereas EPA was metabolized by COX-2 and 5-LOX pathways. Moreover, both fatty acids were able to induce COX-2 expression. When we incubated [(3)H]AA labeled cells with exogenous EPA, we observed that EPA did not modify FBS-induced [(3)H]AA release but that the presence of EPA decreased [(3)H]AA metabolism and therefore PGE(2) synthesis. Moreover, we studied the effect of AA and EPA metabolites on macrophage proliferation. Our results showed that PGE(3) stimulated cell growth with a potency similar to that of PGE(2), whereas LTB(5) was less effective than LTB(4). These data suggest that the effects of EPA on cell growth might be attributable, at least in part, to the marked decrease of eicosanoid release.
Nieves
Diana
D
Department of Physiology, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
Moreno
Juan José
JJ
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism* / Q000494:pharmacology; D002250:Carbon Radioisotopes / Q000378:metabolism; D018929:Cell Culture Techniques; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D015118:Eicosapentaenoic Acid / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D011506:Proteins / Q000032:analysis; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors
D002250:Carbon Radioisotopes; D011506:Proteins; D016718:Arachidonic Acid; D015118:Eicosapentaenoic Acid; D013936:Thymidine