Inhibition of prostaglandin synthesis by nitric oxide in RAW 264.7 macrophages

Multiple effects of nitric oxide (NO) were revealed on the inhibition of pr ostaglandin (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 rele ase of PG from cells with LPS treatment at higher concentrations although i t stimulated the release at 50 muM. PGH synthase (PGHS) activity in the mic rosome fraction of the LPS-treated cells was inhibited by (+/-)-(E)-methyl- 2-[(E) -hydroxyimino]-5-nitro-B-methoxy-3-hexeneamine (NOR 1), another NO-g enerating 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 muM or decreased it at higher concentratio ns. These results suggest that the effect of NO on PGs synthesis in LPS-tre ated macrophage cells is mainly due to the balance of its stimulations of t he transcriptional and/or translational expression of PGHS-2 and the inhibi tion of the induced PGHS-2 activity. (C) 2001 Academic Press.