RRC ID |
56625
|
著者 |
Momozane T, Kawamura T, Itoh Y, Sanosaka M, Sasaki T, Kanzaki R, Ose N, Funaki S, Shintani Y, Minami M, Okumura M, Takemori H.
|
タイトル |
Carnosol suppresses interleukin-6 production in mouse lungs injured by ischemia-reperfusion operation and in RAW264.7 macrophages treated with lipopolysaccharide.
|
ジャーナル |
Biochem Cell Biol
|
Abstract |
Carnosol is a naturally occurring herbal compound, known for its antioxidative properties. We previously found that carnosol protected mouse lungs from ischemia-reperfusion injury in ex vivo cultures. To elucidate the molecular mechanisms underpinning carnosol-mediated lung protection, we analyzed modes of interleukin-6 (IL-6) gene expression, which is associated with lung ischemia-reperfusion injury. Microarray analysis of mouse lungs suggested that IL-6 mRNA levels were elevated in the mouse lungs subjected to clamp-reperfusion, which was associated with elevated levels of other inflammatory modulators, such as activating transcription factor 3 (ATF3). Carnosol pretreatment lowered the IL-6 protein levels in mouse lung homogenates prepared after the clamp-reperfusion. On the other hand, the ATF3 gene expression was negatively correlated with that of IL-6 in RAW264.7 cells. IL-6 mRNA levels and gene promoter activities were suppressed by carnosol in RAW264.7 cells, but rescued by ATF3 knockdown. When RAW264.7 cells were subjected to hypoxia-reoxygenation, carnosol treatment lowered oxygen consumption after reoxygenation, which was coupled with a correlation with a transient production of mitochondrial reactive oxygen species and following ATF3 gene expression. These results suggest that carnosol treatment could be a new strategy for protecting lungs from ischemia-reperfusion injury by modulating the ATF3-IL-6 axis.
|
巻・号 |
96(6)
|
ページ |
769-776
|
公開日 |
2018-12-1
|
DOI |
10.1139/bcb-2017-0339
|
PMID |
29958095
|
MeSH |
Abietanes / pharmacology*
Animals
Cells, Cultured
Dose-Response Relationship, Drug
Interleukin-6 / antagonists & inhibitors*
Interleukin-6 / biosynthesis
Interleukin-6 / genetics
Lipopolysaccharides / pharmacology*
Lung / metabolism*
Lung / pathology
Macrophages / drug effects*
Macrophages / metabolism
Mice
Mice, Inbred C57BL
RAW 264.7 Cells
RNA, Messenger / antagonists & inhibitors
RNA, Messenger / biosynthesis
RNA, Messenger / genetics
Reactive Oxygen Species / analysis
Reactive Oxygen Species / metabolism
Reperfusion Injury / metabolism*
Reperfusion Injury / pathology
|
IF |
2.014
|
引用数 |
0
|
リソース情報 |
ヒト・動物細胞 |
RAW 264(RCB0535) |