Inhibition of Prostaglandin Synthesis by Nitric Oxide in RAW 264.7 Macrophages

Abstract

Multiple effects of nitric oxide (NO) were revealed on the inhibition of prostaglandin (PG) synthesis by a macrophage-like cell line, RAW 264.7 cells, treated with lipopolysaccharide (LPS). NO-generating reagent, N-ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino)ethanamine (NOC 12), inhibited the release of PG from cells with LPS treatment at higher concentrations although it stimulated the release at 50 μM. PGH synthase (PGHS) activity in the microsome fraction of the LPS-treated cells was inhibited by (±)-(E)-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexeneamine (NOR 1), another NO-generating reagent, dose dependently. NOC 12 also dose dependently inhibited PG synthesis from exogenous arachidonic acid in those cells. On the other hand, NOC 12 increased PGHS-2 mRNA, while it increased the PGHS-2 protein at concentrations lower than 200 μM or decreased it at higher concentrations. These results suggest that the effect of NO on PGs synthesis in LPS-treated macrophage cells is mainly due to the balance of its stimulations of the transcriptional and/or translational expression of PGHS-2 and the inhibition of the induced PGHS-2 activity.