| RRC ID |
18636
|
| Author |
Yanagitai M, Itoh S, Kitagawa T, Takenouchi T, Kitani H, Satoh T.
|
| Title |
Carnosic acid, a pro-electrophilic compound, inhibits LPS-induced activation of microglia.
|
| Journal |
Biochem Biophys Res Commun
|
| Abstract |
In the previous studies, we reported that carnosic acid (CA) protects cortical neurons by activating the Keap1/Nrf2 pathway, which activation is initiated by S-alkylation of the critical cysteine thiol of the Keap1 protein by the "electrophilic"quinone-type CA. Here, we found that the pro-electrophilic CA inhibited the in vitro lipopolysaccharide (LPS)-induced activation of cells of the mouse microglial cell line MG6. LPS induced the expression of IL-1β and IL-6, typical inflammatory cytokines released from microglial cells. CA inhibited the NO production associated with a decrease in the level of inducible NO synthase. Neither CA nor LPS affected cell survival at the concentrations used here. These actions of CA seemed to be mediated by induction of phase 2 genes (gclc, gclm, nqo1 and xct). We propose that an inducer of phase 2 genes may be a critical regulator of microglial activation. Thus, CA is a unique pro-electrophilic compound that provides both a protective effect on neurons and an anti-inflammatory one on microglia through induction of phase 2 genes.
|
| Volume |
418(1)
|
| Pages |
22-6
|
| Published |
2012-2-3
|
| DOI |
10.1016/j.bbrc.2011.12.087
|
| PII |
S0006-291X(11)02296-0
|
| PMID |
22214931
|
| MeSH |
Abietanes / pharmacology*
Amino Acid Transport System y+ / genetics
Animals
Cell Line
G2 Phase / drug effects*
G2 Phase / genetics
Glutamate-Cysteine Ligase / genetics
Interleukin-1beta / antagonists & inhibitors
Interleukin-1beta / biosynthesis
Interleukin-6 / antagonists & inhibitors
Interleukin-6 / biosynthesis
Lipopolysaccharides / immunology
Mice
Microglia / drug effects*
Microglia / immunology*
NAD(P)H Dehydrogenase (Quinone) / genetics
Nitric Oxide / antagonists & inhibitors
Nitric Oxide / biosynthesis
Nitric Oxide Synthase Type II / antagonists & inhibitors
Plant Extracts / pharmacology*
|
| IF |
2.985
|
| Times Cited |
25
|
|
WOS Category
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| Human and Animal Cells |
MG6(RCB2403) |
