title: Pseudomonas aeruginosa-induced IL-1β production is inhibited by Sophora flavescens via the NF-κB/inflammasome pathways.
abstract: The proinflammatory cytokine interleukin-1β plays an important role in protecting the host against airway infection; however, it can also trigger a massive influx of neutrophils into the airways, causing tissue damage. Anti-inflammatory treatments are particularly in demand for patients suffering from chronic inflammatory diseases. Sophora flavescens is a traditional herbal medicine used to reduce inflammation, but no study has examined its ability to block IL-1β production. Here, we show that S. flavescens reduced the Pseudomonas aeruginosa-induced expression of IL-1β by lung epithelial cells and macrophages. S. flavescens was also effective at reducing IL-1β production induced by either Staphylococcus aureus or phorbol 12-myristate 13-acetate, indicating that the effect is generalizable to diverse inflammatory stimuli. In addition, S. flavescens blocked the phosphorylation of IKKα/β, key upstream kinases involved in the degradation of IκBα, and the cleavage of caspase-1, a key component of the inflammasome. Thus, this study demonstrates that S. flavescens exerts its anti-inflammatory effects by blocking P. aeruginosa-mediated NF-κB/inflammasome activation and the subsequent production of IL-1β.
authors.affiliation: Department of Biotechnology and Bioinformatics, Korea University, Sejong, 339-700, Republic of Korea.
authors.forename: Jung-Hoon
authors.initials: JH
authors.lastname: Lee
authors.forename: Heesung
authors.initials: H
authors.lastname: Shin
authors.forename: Yong-Jae
authors.initials: YJ
authors.lastname: Kim
authors.forename: Se-Hwan
authors.initials: SH
authors.lastname: Paek
authors.forename: Shouguang
authors.initials: S
authors.lastname: Jin
authors.forename: Un-Hwan
authors.initials: UH
authors.lastname: Ha
mesh_terms: D020170:Caspase 1 / Q000378:metabolism; D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000276:immunology* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D029909:Sophora / Q000378:metabolism; D013211:Staphylococcus aureus / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D020672:I-kappa B Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; C016658:phorbolol myristate acetate; D020170:Caspase 1; D013755:Tetradecanoylphorbol Acetate