| RRC ID |
44966
|
| 著者 |
Jambalganiin U, Tsolmongyn B, Koide N, Odkhuu E, Naiki Y, Komatsu T, Yoshida T, Yokochi T.
|
| タイトル |
A novel mechanism for inhibition of lipopolysaccharide-induced proinflammatory cytokine production by valproic acid.
|
| ジャーナル |
Int Immunopharmacol
|
| Abstract |
The inhibitory effect of valproic acid (VPA) on lipopolysaccharide (LPS)-induced inflammatory response was studied by using mouse RAW 264.7 macrophage-like cells. VPA pretreatment attenuated LPS-induced phosphorylation of phosphatidylinositol 3-kinase (PI3K) and Akt, but not nuclear factor (NF)-κB and mitogen-activated protein kinases. VPA reduced phosphorylation of MDM2, an ubiquitin ligase and then prevented LPS-induced p53 degradation, followed by enhanced p53 expression. Moreover, p53 small interfering RNA (siRNA) abolished the inhibitory action of VPA on LPS-induced NF-κB p65 transcriptional activation and further LPS-induced tumor necrosis factor (TNF)-α and interleukin (IL)-6 production. VPA prevented LPS-induced degradation of phosphatase and tensin homologue deleted on chromosome ten (PTEN) and up-regulated the PTEN expression. Taken together, VPA was suggested to down-regulate LPS-induced NF-κB-dependent transcriptional activity via impaired PI3K/Akt/MDM2 activation and enhanced p53 expression. A detailed mechanism for inhibition of LPS-induced inflammatory response by VPA is discussed.
|
| 巻・号 |
20(1)
|
| ページ |
181-7
|
| 公開日 |
2014-5-1
|
| DOI |
10.1016/j.intimp.2014.02.032
|
| PII |
S1567-5769(14)00086-1
|
| PMID |
24631367
|
| MeSH |
Animals
Anti-Inflammatory Agents / pharmacology*
Cell Line
Interleukin-6 / antagonists & inhibitors*
Interleukin-6 / metabolism
Lipopolysaccharides
Mice
Mitogen-Activated Protein Kinases / metabolism
NF-kappa B / metabolism
PTEN Phosphohydrolase / metabolism
Phosphatidylinositol 3-Kinases / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Toll-Like Receptor 4 / metabolism
Tumor Necrosis Factor-alpha / antagonists & inhibitors*
Tumor Necrosis Factor-alpha / metabolism
Tumor Suppressor Protein p53 / metabolism
Valproic Acid / pharmacology*
|
| IF |
3.943
|
| 引用数 |
10
|
|
WOS 分野
|
PHARMACOLOGY & PHARMACY
IMMUNOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
RAW 264(RCB0535) |
