RRC ID 56625
Author Momozane T, Kawamura T, Itoh Y, Sanosaka M, Sasaki T, Kanzaki R, Ose N, Funaki S, Shintani Y, Minami M, Okumura M, Takemori H.
Title Carnosol suppresses interleukin-6 production in mouse lungs injured by ischemia-reperfusion operation and in RAW264.7 macrophages treated with lipopolysaccharide.
Journal 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.
Volume 96(6)
Pages 769-776
Published 2018-12
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
Times Cited 0
Human and Animal Cells RAW 264(RCB0535)