Nitric oxide inhibits lipopolysaccharide-induced inducible nitric oxide synthase expression and its own production through the cGMP signaling pathway in murine microglia BV-2 cells

The present study examined the effect of the nitric oxide (no) donor noc18 on lipopolysaccharide (lps)-induced no production to investigate a regulation mechanism of no production by microglial cells. lps increased the levels of no and inducible no synthase (inos) protein in bv-2 murine microglial cells in a concentration-dependent manner. pretreatment with noc18 for 24 h concentration-dependently attenuated the lps-induced inos protein expression and no production. the inhibitory effect of noc18 on lps-induced no production was partially blocked by ly83583,a soluble guanylate cyclase inhibitor. pretreatment with dibutyryl guanosine-3′,5′-cyclic monophosphate (dbcgmp),a cell-permeable cgmp analogue,for 24 h attenuated partially lps-induced inos protein expression and no production. furthermore,the effects of lps on inos and no production were inhibited by the c-jun n-terminal kinase (jnk) inhibitor sp600125,and lps-induced phosphorylation of jnk and c-jun was inhibited by noc18 and dbcgmp. these results suggest that no production by microglial cells is controlled by a negative feedback mechanism via the no/cgmp signaling pathway. © 2010 the japanese pharmacological society.