Korean J Physiol Pharmacol.  2017 Jul;21(4):449-456. 10.4196/kjpp.2017.21.4.449.

Beauvericin, a cyclic peptide, inhibits inflammatory responses in macrophages by inhibiting the NF-κB pathway

• Yoo S
• Kim MY
• Cho JY

• KMID: 2384459
• DOI: http://doi.org/10.4196/kjpp.2017.21.4.449

Abstract

Beauvericin (BEA), a cyclic hexadepsipeptide produced by the fungus Beauveria bassiana, is known to have anti-cancer, anti-inflammatory, and anti-microbial actions. However, how BEA suppresses macrophage-induced inflammatory responses has not been fully elucidated. In this study, we explored the anti-inflammatory properties of BEA and the underlying molecular mechanisms using lipopolysaccharide (LPS)-treated macrophage-like RAW264.7 cells. Levels of nitric oxide (NO), mRNA levels of transcription factors and the inflammatory genes inducible NO synthase (iNOS) and interleukin (IL)-1, and protein levels of activated intracellular signaling molecules were determined by Griess assay, semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), luciferase reporter gene assay, and immunoblotting analysis. BEA dose-dependently blocked the production of NO in LPS-treated RAW264.7 cells without inducing cell cytotoxicity. BEA also prevented LPS-triggered morphological changes. This compound significantly inhibited nuclear translocation of the NF-κB subunits p65 and p50. Luciferase reporter gene assays demonstrated that BEA suppresses MyD88-dependent NF-κB activation. By analyzing upstream signaling events for NF-κB activation and overexpressing Src and Syk, these two enzymes were revealed to be targets of BEA. Together, these results suggest that BEA suppresses NF-κB-dependent inflammatory responses by suppressing both Src and Syk.

Keyword

Anti-inflammatory activity; Beauvericin; NF-κB; Src; Syk

MeSH Terms

Beauveria
Fungi
Genes, Reporter
Immunoblotting
Interleukins
Luciferases
Macrophages*
Nitric Oxide
Nitric Oxide Synthase
RNA, Messenger
Transcription Factors
Interleukins
Luciferases
Nitric Oxide
Nitric Oxide Synthase
RNA, Messenger
Transcription Factors