Sodium butyrate modulates innate immunity to Enteropathogens
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1
University College London, Institute of Child Health, United Kingdom
Background
Sodium butyrate (SB), a short chain fatty acid produced by anaerobic gut bacteria is a major energy source for intestinal epithelial cells (IECs). SB exerts anti-inflammatory effects and inhibits the development of colon cancer through mechanisms that are not completely understood. We hypothesised that SB may modulate and promote host defence in response to enteropathogens implicated in Diarrheal and Inflammatory Bowel Diseases.
Methods
THP-1 monocytes were pre-treated for 12 hours with SB (0.5, 1 and 5mM), the pan-histone deacetylase inhibitor trichostatin-A (TSA) (10, 50 and 100nM) and 5-aza-dC, an inhibitor of DNA-methyltransferase (0.5, 1 and 5μM). Cells were then infected with Adherent invasive E.coli (AIEC) (MOI = 10), Campylobacter jejuni (CJ) (MOI = 100) and Salmonella typhi (S. typhi) (MOI = 5) for 6 hours and supernatants were analyzed for the presence of TNF-α, IL-8 and IL-10 cytokines by ELISA.
Results
NaBu (even at a low concentration 0.5mM) but not TSA or AZA led to enhancement of the IL-8 response to Salmonella typhi. Pre-treatment with all three inhibitors led to a marked suppression in TNF-α production (>50%). The presence of NaBu, but not TSA or AZA, led to enhanced IL-10 cytokine levels following infection (Fig. 3). The suppressive effect of NaBu on TNF-α was comparable between all enteropathogens, whereas enhancement of IL-10 production was more dramatic in the E. coli infection model (AIEC, EPEC).
Conclusion
Our findings show that NaBu can enhance the innate immune response to bacterial infection, increasing the production of the key IL-8 chemokine and the anti-inflammatory cytokine IL-10. These effects are independent of the inhibition of histone-modifying enzymes or DNA methylation events. In ongoing work, we aim to characterise the molecular events that underpin these unique properties of NaBu and its potential benefits to microbial response.
Keywords:
NaBu,
IL-10,
Enteropathogens,
Macrophages,
innate immunity
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Innate immunity
Citation:
Milioris
E,
Iebba
V,
Klein
NK and
Bajaj-Elliott
M
(2013). Sodium butyrate modulates innate immunity to Enteropathogens.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00632
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Received:
12 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Mr. Enea Milioris, University College London, Institute of Child Health, London, United Kingdom, enea.milioris.09@ucl.ac.uk