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
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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.
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.
참고문헌 (20)
- Alpsoy E, "Behcet's disease: a comprehensive review with a focus on epidemiology, etiology and clinical features, and management of mucocutaneous lesions", J Dermatol, 43, pp.620~632 (2016)[DOI]
- Loftus RM, "Immunometabolism: cellular metabolism turns immune regulator", J Biol Chem, 291, pp.1~10 (2016)[DOI]
- Seki SM, "Lineage-specific metabolic properties and vulnerabilities of T cells in the demyelinating central nervous system", J Immunol, 198, pp.4607~4617 (2017)[DOI]
- Okano T, "3-bromopyruvate ameliorate autoimmune arthritis by modulating Th17", Treg cell differentiation and suppressing dendritic cell activation, 2017, pp.7, 42412~
- Schonfeld P, "Short- and medium-chain fatty acids in energy metabolism: the cellular perspective", J Lipid Res, 57, pp.943~954 (2016)[DOI]
- Correa-Oliveira R, "Regulation of immune cell function by short-chain fatty acids", Clin Transl Immunology, 5, pp.e73~ (2016)[DOI]
- Consolandi C, "Behcet's syndrome patients exhibit specific microbiome signature", Autoimmun Rev, 14, pp.269~276 (2015)[DOI]
- Ko YH, "Advanced cancers: eradication in all cases using 3-bromopyruvate therapy to deplete ATP", Biochem Biophys Res Commun, 324, pp.269~275 (2004)[DOI]
- Lachmandas E, "Microbial stimulation of different Toll-like receptor signalling pathways induces diverse metabolic programmes in human monocytes", Nat Microbiol, 2, pp.16246~ (2016)
- Nastasi C, "The effect of short-chain fatty acids on human monocyte-derived dendritic cells", Sci Rep, 5, pp.16148~ (2015)[DOI]
- Yuan X, "Differential effects of short chain fatty acids on endothelial Nlrp3 inflammasome activation and neointima formation: antioxidant action of butyrate", Redox Biol, 16, pp.21~31 (2018)[DOI]
- Saemann MD, "Bacterial metabolite interference with maturation of human monocyte-derived dendritic cells", J Leukoc Biol, 71, pp.238~246 (2002)
- Chen G, "Sodium butyrate inhibits inflammation and maintains epithelium barrier integrity in a TNBS-induced inflammatory bowel disease mice model", EBioMedicine, 30, pp.317~325 (2018)[DOI]
- Geri G, "Critical role of IL-21 in modulating TH17 and regulatory T cells in Behcet disease", J Allergy Clin Immunol, 128, pp.655~664 (2011)[DOI]
- Na SY, "Up-regulation of Th17 and related cytokines in Behcet's disease corresponding to disease activity", Clin Exp Rheumatol, 31(3 Suppl 77), pp.32~40 (2013)
- Arpaia N, "Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation", Nature, 504, pp.451~455 (2013)[DOI]
- Furusawa Y, "Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells", Nature, 504, pp.446~450 (2013)[DOI]
- Ko YH, "A translational study "case report" on the small molecule "energy blocker" 3-bromopyruvate (3BP) as a potent anticancer agent: from bench side to bedside", J Bioenerg Biomembr, 44, pp.163~170 (2012)[DOI]
- Ang Z, "Human and mouse monocytes display distinct signalling and cytokine profiles upon stimulation with FFAR2", FFAR3 short-chain fatty acid receptor agonists, 2016, pp.6, 34145~
- Ji J, "Microbial metabolite butyrate facilitates M2 macrophage polarization and function", Sci Rep, 6, pp.24838~ (2016)[DOI]