Beauvericin, a cyclic peptide, inhibits inflammatory responses in macrophages by inhibiting the NF-κB pathway.
10.4196/kjpp.2017.21.4.449
- Author:
Sulgi YOO
1
;
Mi Yeon KIM
;
Jae Youl CHO
Author Information
1. Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Korea. jaecho@skku.edu
- Publication Type:Original Article
- Keywords:
Anti-inflammatory activity;
Beauvericin;
NF-κB;
Src;
Syk
- MeSH:
Beauveria;
Fungi;
Genes, Reporter;
Immunoblotting;
Interleukins;
Luciferases;
Macrophages*;
Nitric Oxide;
Nitric Oxide Synthase;
RNA, Messenger;
Transcription Factors
- From:The Korean Journal of Physiology and Pharmacology
2017;21(4):449-456
- CountryRepublic of Korea
- Language:English
-
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.
