Ann Dermatol.  2018 Oct;30(5):566-574. 10.5021/ad.2018.30.5.566.

The Suppressive Effect of Butyrate and Bromopyruvate on Inflammatory Cytokine Production and Short Chain Fatty Acid Receptor Expression by Blood Mononuclear Cells in Patients with Behçet's Disease

• Yun SJ
• Kim K
• Lee ES
• Park S

• KMID: 2419747
• DOI: http://doi.org/10.5021/ad.2018.30.5.566

Abstract

BACKGROUND
Controlling inflammation is a therapeutic goal of various autoimmune/autoinflammatory diseases including Behçet's disease (BD). The immunomodulatory effect of metabolites or metabolic analogs such as butyrate and 3-bromopyruvate has been observed in animal disease models.
OBJECTIVE
We attempted to evaluate the effect of butyrate and 3-bromopyruvate on the inflammatory cytokine production by peripheral blood mononuclear cells (PBMCs) isolated from patients with mucocutaneous involvement of BD.
METHODS
PBMCs isolated from 11 patients with BD and 10 healthy controls were stimulated with lipopolysaccharide in the presence of butyrate or 3-bromopyruvate. Butyrate receptor and cytokine messenger ribonucleic acid (mRNA) expression was analyzed by real-time reverse transcription polymerase chain reaction. Cytokine secretion was assessed by enzyme-linked immunosorbent assay. PBMCs survival was analyzed by flow cytometry.
RESULTS
Bromopyruvate or butyrate treatment suppressed inflammatory cytokine production in PBMCs from all our subjects. Bromopyruvate also reduced PBMCs survival while butyrate did not. As the effect of butyrate was slightly greater in BD patients than in healthy controls, we analyzed butyrate receptor expression and found that lipopolysaccharide-induced free fatty acid receptor 2 mRNA level in PBMCs was higher in BD patients than in controls.
CONCLUSION
We propose bromopyruvate and butyrate as supplementary therapeutic candidates to control inflammation in patients with BD.

Keyword

Autoimmune diseases; Butyrates; Glycolysis; Inflammation

MeSH Terms

Autoimmune Diseases
Butyrates*
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Glycolysis
Humans
Inflammation
Polymerase Chain Reaction
Reverse Transcription
RNA
RNA, Messenger
Butyrates
RNA
RNA, Messenger

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