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: Junpei Yokoigawa, Kyoko Morimoto, Yoshihito Shiono, Shota Uesugi, Ken-ichi Kimura, Takao Kataoka
• Journal: The Journal of antibiotics (J Antibiot (Tokyo)) Vol. 68 Issue 2 Pg. 71-5 (Feb 2015) ISSN: 1881-1469 [Electronic] England
• PMID: 25118107 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NF-kappa B
• Pyrones
• Tumor Necrosis Factor-alpha
• allantopyrone A
• Intercellular Adhesion Molecule-1
• Luciferases, Firefly
• I-kappa B Kinase

Topics

• Animals
• Cell Line, Tumor
• Gene Expression Regulation (drug effects)
• Genes, Reporter (genetics)
• Humans
• I-kappa B Kinase (metabolism)
• Intercellular Adhesion Molecule-1 (genetics)
• Luciferases, Firefly (genetics)
• Lung Neoplasms (metabolism)
• NF-kappa B (metabolism)
• Phosphorylation (drug effects)
• Pyrones (pharmacology)
• Signal Transduction (drug effects)
• Tumor Necrosis Factor-alpha (metabolism)