title: Allantopyrone A, an α-pyrone metabolite from an endophytic fungus, inhibits the tumor necrosis factor α-induced nuclear factor κB signaling pathway.
abstract: Tumor necrosis factor α (TNF-α) induces the activation of transcription factor nuclear factor κB (NF-κB), which upregulates a variety of genes, including the gene encoding intercellular adhesion molecule-1 (ICAM-1). Allantopyrone A, a recently identified α-pyrone metabolite from an endophytic fungus, was found to inhibit the TNF-α-induced expression of ICAM-1 in human lung carcinoma A549 cells. Allantopyrone A also inhibited the TNF-α-induced luciferase expression of an NF-κB-responsive reporter. In the NF-κB signaling pathway, allantopyrone A inhibited the nuclear translocation of NF-κB subunits as well as the phosphorylation and subsequent degradation of the inhibitor of NF-κB (IκB) α proteins. By contrast, allantopyrone A did not directly affect the catalytic activity of active IκB kinase β. These findings indicate that allantopyrone A inhibits the NF-κB signaling pathway at a step upstream of IκBα phosphorylation.
authors.affiliation: Department of Applied Biology, Kyoto Institute of Technology, Kyoto, Japan.
authors.forename: Junpei
authors.initials: J
authors.lastname: Yokoigawa
authors.affiliation: Department of Applied Biology, Kyoto Institute of Technology, Kyoto, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Morimoto
authors.affiliation: Department of Bioresource Engineering, Faculty of Agriculture, Yamagata University, Yamagata, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Shiono
authors.affiliation: The United Graduate School of Agricultural Sciences, Iwate University, Iwate, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Uesugi
authors.affiliation: The United Graduate School of Agricultural Sciences, Iwate University, Iwate, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Kimura
authors.affiliation: Department of Applied Biology, Kyoto Institute of Technology, Kyoto, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Kataoka
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000187:drug effects*; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D049409:Luciferases, Firefly / Q000235:genetics; D008175:Lung Neoplasms / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011753:Pyrones / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D011753:Pyrones; D014409:Tumor Necrosis Factor-alpha; C550113:allantopyrone A; D018799:Intercellular Adhesion Molecule-1; D049409:Luciferases, Firefly; D051550:I-kappa B Kinase