| RRC ID |
58735
|
| 著者 |
Ogawa K, Yagi T, Guo T, Takeda K, Ohguchi H, Koyama H, Aotani D, Imaeda K, Kataoka H, Tanaka T.
|
| タイトル |
Pemafibrate, a selective PPARα modulator, and fenofibrate suppress microglial activation through distinct PPARα and SIRT1-dependent pathways.
|
| ジャーナル |
Biochem Biophys Res Commun
|
| Abstract |
Pemafibrate, a selective peroxisome proliferator-activated receptor (PPAR) α modulator, is a new drug that specifically modulates PPARα conformation and co-activator recruitment, thereby lowers plasma triglycerides with less off-target effects. Classical PPARα ligands such as fenofibrate suppress inflammatory cells including microglia. However, effects of pemafibrate on microglia have never been addressed. Here we show that pemafibrate, like other PPARα ligands, potently suppressed NF-κB phosphorylation and cytokine expression in microglial cells. PPARα knockdown significantly amplified LPS-induced cytokine expression. Pemafibrate-induced suppression of IL-6 expression was reversed by PPARα knockdown. However, suppression by fenofibrate was not reversed by PPARα knockdown but by Sirtuin 1 (SIRT1) knockdown. In conclusion, pemafibrate and fenofibrate similarly suppresses microglial activation but through distinct PPARα and SIRT1-dependet pathways.
|
| 巻・号 |
524(2)
|
| ページ |
385-391
|
| 公開日 |
2020-4-2
|
| DOI |
10.1016/j.bbrc.2020.01.118
|
| PII |
S0006-291X(20)30195-9
|
| PMID |
32005522
|
| MeSH |
Animals
Anti-Inflammatory Agents / pharmacology*
Benzoxazoles / pharmacology*
Butyrates / pharmacology*
Cell Line
Inflammation / drug therapy
Inflammation / metabolism
Male
Mice
Mice, Inbred C57BL
Microglia / drug effects*
Microglia / metabolism
PPAR alpha / metabolism*
Signal Transduction / drug effects*
Sirtuin 1 / metabolism*
|
| IF |
2.985
|
| 引用数 |
0
|
| リソース情報 |
| ヒト・動物細胞 |
MG6(RCB2403) |
