Reference - Detail
RRC ID | 61284 |
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Author | Etoh T, Kim YP, Tanaka H, Hayashi M. |
Title | Anti-inflammatory effect of berkeleyacetal C through the inhibition of interleukin-1 receptor-associated kinase-4 activity. |
Journal | Eur J Pharmacol |
Abstract |
Berkeleyacetal C (BAC) isolated from Penicillium sp. which had isolated from a soil sample collected in Fukushima, inhibited NO production and induction of iNOS protein in RAW264.7 cells stimulated by the Toll-like receptor (TLR) 2 ligand, peptidoglycan (PGN) or TLR4 ligand, lipopolysaccharide (LPS). The other inflammatory mediator production by these stimulators was also suppressed by BAC in a concentration-dependent manner. BAC inhibited LPS- or PGN-activated nuclear translocation of nuclear factor (NF)-κB and MyD88-dependent signaling molecules. However, it showed no effect on LPS-induced nuclear translocation of interferon regulatory factor (IRF)-3, a MyD88-independent signaling molecule. To clarify the mechanistic basis for BAC ability to inhibit translocation of NF-κB and activated MyD88-dependent signaling molecules, we examined interleukin-1 receptor-associated kinase (IRAK)-4, existing to the most upstream on MyD88-dependent signaling molecules, in vitro kinase assay. BAC suppressed IRAK-4 kinase activity in a concentration-dependent manner. These findings suggest that BAC inhibits LPS- and PGN- induced NO production and iNOS expression by decreasing the level of the translocating of NF-κB in nuclear through inhibiting the kinase activity of IRAK-4 in inflammatory cells. |
Volume | 698(1-3) |
Pages | 435-43 |
Published | 2013-1-5 |
DOI | 10.1016/j.ejphar.2012.10.038 |
PII | S0014-2999(12)00907-7 |
PMID | 23127497 |
MeSH | Active Transport, Cell Nucleus / drug effects Animals Anti-Inflammatory Agents, Non-Steroidal / pharmacology* Cell Line Cell Nucleus / drug effects Cell Nucleus / metabolism Cyclooxygenase 2 / metabolism Dinoprostone / biosynthesis Gene Expression Regulation, Enzymologic / drug effects Interferon Regulatory Factor-3 / metabolism Interleukin-1 Receptor-Associated Kinases / antagonists & inhibitors* Interleukin-1 Receptor-Associated Kinases / metabolism Lipopolysaccharides / pharmacology Macrophages, Peritoneal / drug effects Macrophages, Peritoneal / metabolism Male Mice NF-kappa B / metabolism Nitric Oxide / biosynthesis Nitric Oxide Synthase Type II / metabolism Peptidoglycan / pharmacology Rats Rats, Wistar Signal Transduction / drug effects Terpenes / pharmacology* Toll-Like Receptors / metabolism Tumor Necrosis Factor-alpha / biosynthesis |
IF | 3.263 |
Resource | |
Human and Animal Cells | RAW 264(RCB0535) |