Prostaglandin E2 synthesis is differentially affected by reactive nitrogen intermediates in cultured rat microglia...

We studied the effects of nitric oxide (NO) on prostanoid production, cyclooxygenase (COX-2) expression and [3H]arachidonic acid (AA) release in RAW 264.7 macrophagic cells and rat microglial primary cultures. Inhibition of NO synthesis enhanced microglial prostanoid production without affecting that of RAW 264.7 cells. Both 3-morpholinosydnonimine (SIN-1), (which, by releasing NO and superoxide, leads to the formation of peroxynitrite), and S-nitroso-N-acetylpenicillamine (SNAP), (which releases only NO), inhibited microglial prostanoid production, by preventing COX-2 expression. In contrast, in RAW 264.7 cells, SIN-1 enhanced both basal and LPS-stimulated prostanoid production by upregulating COX-2, while SNAP stimulated basal production and slightly inhibited the LPS-induced production, as a cumulative result of enhanced AA release and depressed COX-2 expression. Thus, reactive nitrogen intermediates can influence prostanoid production at distinct levels and in different way in the two cell types, and results obtained with RAW 264.7 cells can not be extrapolated to microglia.