Suppression of Prostaglandin Synthesis by Arachidonic Acid or Eicosapentaenoic Acid in a Macrophage-Like Cell Line, RAW 264.7, Treated with LPS

抄録

In a mouse macrophage-like cell line, RAW 264.7, increasing the arachidonic acid (AA) content, by culturing cells with AA, caused profound AA release, irrespective of the lipopolysaccharide (LPS)-treatment, while lowering the AA content, by culturing cells with eicosapentaenoic acid (EPA), decreased it compared with the level in non-modified control cells. However, the release of prostaglandin D₂ (PGD₂), which had been generated from AA in response to LPS-treatment, was significantly decreased in both AA- and EPA-treated cells. Furthermore, although the amount of PG endoperoxide synthase-2 (PGHS-2) increased following LPS-treatment in all cases, both AA- and EPA-treatment caused a reduction of PGHS activity in LPS-treated cell lysates. Also, the addition of EPA or preincubation with AA in an in vitro PGHS assay system involving an LPS-treated, un-modified macrophage lysate, resulted in rapid inhibition of PGHS activity. These results suggest that both AA- and EPA-treatment inhibit PGD₂ synthesis by inactivating PGHS-2 without affecting induction of the protein, and that the increase or decrease in AA content following AA- or EPA-treatment correlates simply with the level of AA release but not with that of PGD₂ formation.