Nuclear factor-kappaB/signal transducers and activators of transcription-1-mediated inflammatory responses in lipopolysaccharide-activated macrophages are a major inhibitory target of kahweol, a coffee diterpene.
Diterpene kahweol, one of the major components in coffee, has anti-cancer, anti-oxidative, and anti-inflammatory activity. In this study, we explored the molecular mechanism of the anti-inflammatory activity of kahweol. Lipopolysaccharide (LPS)-activated RAW264.7 cells were used to explore the modulatory role of kahweol on nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production and the activation of signaling proteins and transcription factors using immunoblotting and reverse transcription-polymerase chain reaction (RT-PCR). Kahweol diminished both the production of NO and PGE(2) and the mRNA expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2. Interestingly, this compound suppressed the phospho-signal transducers and activators of transcription (STAT)-1 and p65/nuclear factor (NF)-kappaB levels in the nucleus but not c-Jun and c-fos. In conjunction, the phosphorylation of Akt and Janus kinase (JAK)2 also decreased. Therefore, our data suggest that kahweol in coffee may be an anti-inflammatory modulator with NF-kappaB/STAT-1-targeted inhibitory properties in LPS-activated RAW264.7 cells.
Shen
Ting
T
School of Bioscience and Biotechnology, Kangwon National University, Chuncheon, Korea.
Park
Yung Chul
YC
Kim
Seong Hwan
SH
Lee
Jaehwi
J
Cho
Jae Youl
JY
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D003069:Coffee / Q000737:chemistry*; D017931:DNA Primers; D015232:Dinoprostone / Q000096:biosynthesis; D004224:Diterpenes / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000502:physiology*
D003069:Coffee; D017931:DNA Primers; D004224:Diterpenes; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D009569:Nitric Oxide; C053401:kahweol; D052247:Nitric Oxide Synthase Type II; D015232:Dinoprostone