biostudies-literatureHe Zthe fund of Scholar Research of Kagoshima Universitye2108https://www.ebi.ac.uk/biostudies/studies/S-EPMC11680972biostudies-literatureUnknown51(1)The mitogen-activated protein kinase kinase 4 (MKK4), a member of the MAP kinase kinase family, directly phosphorylates and activates the c-Jun NH2-terminal kinases (JNK), in response to proinflammatory cytokines and cellular stresses. Regulation of the MKK4 activity is considered to be a novel approach for the prevention and treatment of inflammation. The aim of this study was to identify whether fisetin, a potential anti-inflammatory compound, targets MKK4-JNK cascade to inhibit lipopolysaccharide (LPS)-stimulated inflammatory response. RAW264 macrophage pretreated with fisetin following LPS stimulation was used as a cell model to investigate the transactivation and expression of related-inflammatory genes by transient transfection assay, electrophoretic mobility shift assay (EMSA), or eBioFactors (Oxford, England)Fisetin is a selective adenosine triphosphate-competitive inhibitor for mitogen-activated protein kinase kinase 4 to inhibit lipopolysaccharide-stimulated inflammation.PMC1168097270030117Uto TPan XYang YHe ZKumamoto TXie KTanigawa SWu SHou DXSakao KKomatsu MfalseFisetin is a selective adenosine triphosphate-competitive inhibitor for mitogen-activated protein kinase kinase 4 to inhibit lipopolysaccharide-stimulated inflammation.The mitogen-activated protein kinase kinase 4 (MKK4), a member of the MAP kinase kinase family, directly phosphorylates and activates the c-Jun NH2-terminal kinases (JNK), in response to proinflammatory cytokines and cellular stresses. Regulation of the MKK4 activity is considered to be a novel approach for the prevention and treatment of inflammation. The aim of this study was to identify whether fisetin, a potential anti-inflammatory compound, targets MKK4-JNK cascade to inhibit lipopolysaccharide (LPS)-stimulated inflammatory response. RAW264 macrophage pretreated with fisetin following LPS stimulation was used as a cell model to investigate the transactivation and expression of related-inflammatory genes by transient transfection assay, electrophoretic mobility shift assay (EMSA), or e2025-01-01T00:00:00Z2025 Jan-Feb2026-04-13T03:23:09.824Z2025-04-04T02:48:36.665ZS-EPMC116809723908758710.1002/biof.2108