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.
Yoshioka
Yasuhiro
Y
Department of Pharmacotherapeutics, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, Japan.
Takeda
Nobuo
N
Yamamuro
Akiko
A
Kasai
Atsushi
A
Maeda
Sadaaki
S
D000818:Animals; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000502:physiology*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000201:enzymology* / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D008070:Lipopolysaccharides; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D006152:Cyclic GMP