Suppression of prostaglandin synthesis by arachidonic acid or eicosapentaenoic acid in a macrophage-like cell line, RAW 264.7, treated with LPS.
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.
Tanaka
Y
Y
Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Tokyo, Japan.
Otsuji
A
A
Amano
F
F
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D002461:Cell Line, Transformed; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D004790:Enzyme Induction; D050356:Lipid Metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D011863:Radioimmunoassay
D008070:Lipopolysaccharides; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D016718:Arachidonic Acid; D015118:Eicosapentaenoic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D015230:Prostaglandin D2