Sodium butyrate inhibits the NF-kappa B signaling pathway and histone deacetylation, and attenuates experimental colitis in an IL-10 independent manner

Butyrate is a bacterial metabolite of dietary fiber in the colon that has been used to treat inflammatory disease. However, the effect of oral supplementation with butyrate on colitis has not been fully explored. We evaluated the effects of and mechanisms underlying oral supplementation with butyrat...

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Bibliographic Details
Published in:International immunopharmacology 2017-10, Vol.51, p.47-56
Main Authors: Lee, Changhyun, Kim, Byeong Gwan, Kim, Jee Hyun, Chun, Jaeyoung, Im, Jong Pil, Kim, Joo Sung
Format: Article
Language:English
Subjects:
Acetylation
Animal models
Animals
Anti-Inflammatory Agents - therapeutic use
Attenuation
Bacteria
Biodegradation
Butyrates
Butyric Acid - therapeutic use
Chemical compounds
Colitis
Colitis - drug therapy
Colon
Cytokines
Deacetylation
Deoxyribonucleic acid
Dextran
Dextran Sulfate
Dietary fiber
Dietary supplements
Disease Models, Animal
DNA
Histone Deacetylases - metabolism
Histone deactylase inhibitors
Histone H3
Humans
Inflammatory bowel disease
Inflammatory bowel diseases
Interleukin 10
Interleukin 12
Interleukin 6
Interleukin 8
Interleukin-10 - genetics
Interleukin-10 - metabolism
Lipopolysaccharides
Lipopolysaccharides - immunology
Macrophage Activation
Macrophages
Macrophages - immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
NF-kappa B
NF-kappa B - metabolism
NF-κB protein
Peritoneum
Pharmacology
Phosphorylation
RAW 264.7 Cells
Signal Transduction
Signaling
Sodium
Sodium butyrate
Sulfates
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Summary:Butyrate is a bacterial metabolite of dietary fiber in the colon that has been used to treat inflammatory disease. However, the effect of oral supplementation with butyrate on colitis has not been fully explored. We evaluated the effects of and mechanisms underlying oral supplementation with butyrate on experimental murine colitis. In an in vitro study, we found that LPS induced the secretion of cytokines (i.e., IL-8 in COLO 205; TNF-α, IL-6, IL-12, and IL-10 in RAW 264.7; and TNF-α, IL-6 and IL-12 in peritoneal macrophages obtained from IL-10-deficient [IL-10−/−] mice). Butyrate (100μM and 500μM) inhibited pro-inflammatory cytokine production (i.e., IL-8 in COLO205 and TNF-α, IL-6 and IL-12 in macrophages) but promoted anti-inflammatory cytokine (i.e., IL-10) production in RAW264.7 cells. Butyrate attenuated both the LPS-induced degradation/phosphorylation of IκBα and DNA binding of NF-κB and enhanced histone H3 acetylation. To confirm that butyrate played a protective role in colitis, an acute colitis model was induced using dextran sulfate sodium (DSS) and a chronic colitis model was induced in IL-10−/− mice. The administration of oral butyrate (100mg/kg) significantly improved histological scores in both colitis models, including the IL-10−/− mice. In immunohistochemical staining, IκBα phosphorylation was attenuated, and histone H3 acetylation was reversed in the treated colons of both colitis models. Our results indicate that oral supplementation with butyrate attenuates experimental murine colitis by blocking NF-κB signaling and reverses histone acetylation. These anti-colitic effects of butyrate were IL-10-independent. Butyrate may therefore be a therapeutic agent for colitis. [Display omitted] •Butyrate inhibits the production of TNF-α, IL-6 and IL-12 in macrophages.•Butyrate inhibits NF-κB signaling and histone deacetylation in IEC and macrophages.•Oral supplementation with butyrate suppressed colitis, even in IL-10−/− mice.•Butyrate attenuated IκBα phosphorylation and histone H3 deacetylation in the colon.•The anti-inflammatory effect of butyrate is IL-10 independent.
ISSN:1567-5769
1878-1705
DOI:10.1016/j.intimp.2017.07.023