Conjugated linoleic acid reduces arachidonic acid content and PGE2 synthesis in murine keratinocytes

Dietary conjugated linoleic acid (CLA) is associated with decreased 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced tumor promotion in mouse skin. In addition, CLA decreases TPA-induced prostaglandin E synthesis and ornithine decarboxylase activity in cultured keratinocytes compared with linoleic acid (LA) and arachidonic acid (AA). When LA or CLA was added to keratinocyte cell cultures, the amounts of each of these cellular fatty acids increased significantly in a dose-dependent manner. Furthermore, LA treatment was associated with increased cellular AA while the AA content of keratinocytes was reduced when cultures were treated with CLA. Moreover, CLA (16 mu g/ml) was more potent than LA at decreasing the level of C-14-AA incorporated into cellular phosphatidylcholine. In order to determine the effect of CLA on arachidonate-derived PGE(2), the release of C-14-AA and C-14-PGE(2) synthesis was measured in cultures pre-treated with LA/C-14-AA or CLA/C-14-AA for 12 h. The amount of C-14-AA release induced by TPA in CLA/C-14-AA pre-treated cultures was significantly lower than cultures pre-treated with LA/C-14-AA. Furthermore, TPA-induced C-14-PGE(2) was significantly lower in cultures pre-treated with CLA/C-14-AA compared with cultures pre-treated with LA/C-14-AA. The effects of LA and CLA on AA composition of phospholipids and subsequent arachidonate-derived PGE(2) synthesis will provide insight into the anti-promoter mechanisms of CLA. (C) 1998 Elsevier Science Ireland Ltd.