J Pharmacol Sci 2010,
PMID: 20484865
Yoshioka, Yasuhiro; Takeda, Nobuo; Yamamuro, Akiko; Kasai, Atsushi; Maeda, Sadaaki
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.
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Text Mining Data
inducible NO synthase (iNOS) → LPS: "
LPS increased the levels of NO and
inducible NO synthase (iNOS) protein in BV-2 murine microglial cells in a concentration dependent manner
"
iNOS → LPS: "
Pretreatment with NOC18 for 24 h concentration-dependently attenuated the LPS induced iNOS protein expression and NO production
"
iNOS → LPS: "
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
"
c-Jun ⊣ LPS: "
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
"
c-Jun ⊣ iNOS: "
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
"
iNOS — LPS: "
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
"
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