Immune Netw.  2019 Apr;19(2):e9. 10.4110/in.2019.19.e9.

Short-chain Fatty Acids Inhibit Staphylococcal Lipoprotein-induced Nitric Oxide Production in Murine Macrophages

• Park JW
• Kim HY
• Kim MG
• Jeong S
• Yun CH
• Han SH

• KMID: 2444157
• DOI: http://doi.org/10.4110/in.2019.19.e9

Abstract

Staphylococcus aureus, a Gram-positive pathogen, can cause severe inflammation in humans, leading to various life-threatening diseases. The lipoprotein is a major virulence factor in S. aureus-induced infectious diseases and is responsible for excessive inflammatory mediators such as nitric oxide (NO). Short-chain fatty acids (SCFAs) including butyrate, propionate, and acetate are microbial metabolites in the gut that are known to have anti-inflammatory effects in the host. In this study, we investigated the effects of SCFAs on S. aureus lipoprotein (Sa.LPP)-induced NO production in mouse macrophages. Butyrate and propionate, but not acetate, inhibited Sa.LPP-induced production of NO in RAW 264.7 cells and bone marrow-derived macrophages. Butyrate and propionate inhibited Sa.LPP-induced expression of inducible NO synthase (iNOS). However, acetate did not show such effects under the same conditions. Furthermore, butyrate and propionate, but not acetate, inhibited Sa.LPP-induced activation of NF-κB, expression of IFN-β, and phosphorylation of STAT1, which are essential for inducing transcription of iNOS in macrophages. In addition, butyrate and propionate induced histone acetylation at lysine residues in the presence of Sa.LPP in RAW 264.7 cells. Moreover, Sa.LPP-induced NO production was decreased by histone deacetylase (HDAC) inhibitors. Collectively, these results suggest that butyrate and propionate ameliorate the inflammatory responses caused by S. aureus through the inhibition of NF-κB, IFN-β/STAT1, and HDAC, resulting in attenuated NO production in macrophages.

Keyword

Staphylococcus aureus, lipoproteins; Short-chain fatty acid; Nitric oxide; HDAC inhibitors; Macrophage

MeSH Terms

Acetylation
Animals
Butyrates
Communicable Diseases
Diethylpropion
Fatty Acids, Volatile*
Histone Deacetylase Inhibitors
Histone Deacetylases
Histones
Humans
Inflammation
Lipoproteins
Lysine
Macrophages*
Mice
Nitric Oxide Synthase
Nitric Oxide*
Phosphorylation
RAW 264.7 Cells
Staphylococcus aureus
Virulence
Butyrates
Diethylpropion
Fatty Acids, Volatile
Histone Deacetylase Inhibitors
Histone Deacetylases
Histones
Lipoproteins
Lysine
Nitric Oxide
Nitric Oxide Synthase