| RRC ID |
44327
|
| 著者 |
Mendjargal A, Odkhuu E, Koide N, Nagata H, Kurokawa T, Nonami T, Yokochi T.
|
| タイトル |
Pifithrin-α, a pharmacological inhibitor of p53, downregulates lipopolysaccharide-induced nitric oxide production via impairment of the MyD88-independent pathway.
|
| ジャーナル |
Int Immunopharmacol
|
| Abstract |
The effect of pifithrin (PFT)-α, a pharmacological inhibitor of p53, on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophage-like cells was examined. PFT-α inhibited the production of NO but not tumor necrosis factor (TNF)-α in response to LPS. PFT-α inhibited LPS-induced NO production via reduced expression of an inducible NO synthase (iNOS). Moreover, PFT-α inhibited LPS-induced iNOS expression in p53-silenced cells. PFT-α inhibited the production of interferon (IFN)-β, characteristic of the MyD88-independent pathway of LPS signaling, whereas it did not affect the activation of nuclear factor (NF)-κB and mitogen-activated protein kinases in the MyD88-dependent pathway. PFT-α inhibited poly I:C-induced NO production whereas it did not inhibit IFN-β-induced NO production. Further, PFT-α reduced the expression of IFN regulatory factor 3 that leads to the IFN-β production in the MyD88-independent pathway. The most upstream event impaired by PFT-α was the reduced expression of TNF receptor-associated factor (TRAF) 3 in the MyD88-independent pathway. PFT-α also reduced the in vivo expression of iNOS in the livers of mice injected with LPS. Taken together, PFT-α was suggested to inhibit LPS-induced NO production via impairment of the MyD88-independent pathway and attenuated LPS-mediated inflammatory response.
|
| 巻・号 |
15(4)
|
| ページ |
671-8
|
| 公開日 |
2013-4-1
|
| DOI |
10.1016/j.intimp.2013.02.014
|
| PII |
S1567-5769(13)00056-8
|
| PMID |
23454130
|
| MeSH |
Animals
Benzothiazoles / administration & dosage
Benzothiazoles / pharmacology*
Benzothiazoles / therapeutic use
Cell Culture Techniques
Cell Line
Cell Survival / drug effects
Chemical and Drug Induced Liver Injury / metabolism
Chemical and Drug Induced Liver Injury / prevention & control
Gene Silencing
Interferon-beta / immunology
Lipopolysaccharides / toxicity*
Macrophages, Peritoneal / drug effects*
Macrophages, Peritoneal / immunology
Macrophages, Peritoneal / metabolism
Male
Mice
Mice, Inbred C57BL
Myeloid Differentiation Factor 88 / metabolism*
Nitric Oxide / antagonists & inhibitors*
Nitric Oxide / biosynthesis
Nitric Oxide Synthase Type II / antagonists & inhibitors
Nitric Oxide Synthase Type II / genetics
RNA, Small Interfering / genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Toluene / administration & dosage
Toluene / analogs & derivatives*
Toluene / pharmacology
Toluene / therapeutic use
Tumor Necrosis Factor-alpha / immunology
Tumor Suppressor Protein p53 / antagonists & inhibitors*
Tumor Suppressor Protein p53 / genetics
|
| IF |
3.943
|
| 引用数 |
8
|
|
WOS 分野
|
PHARMACOLOGY & PHARMACY
IMMUNOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
RAW 264(RCB0535) |
