Redirection of epithelial immune responses by short chain fatty acids through inhibition of histone deacetylases
Short-Chain Fatty Acids (SCFAs) are products of microbial fermentation that are important for intestinal epithelial health. Here we describe that SCFAs have rapid and reversible effects on Toll-like receptor (TLR) responses in epithelial cells. Incubation of HEK293 or HeLa epithelial cells with the...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2015-11-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00554/full |
| _version_ | 1817979524778819584 |
|---|---|
| author | May Young eLin Marcel Robert de Zoete Jos P.M. van Putten Karin eStrijbis |
| author_facet | May Young eLin Marcel Robert de Zoete Jos P.M. van Putten Karin eStrijbis |
| author_sort | May Young eLin |
| collection | DOAJ |
| description | Short-Chain Fatty Acids (SCFAs) are products of microbial fermentation that are important for intestinal epithelial health. Here we describe that SCFAs have rapid and reversible effects on Toll-like receptor (TLR) responses in epithelial cells. Incubation of HEK293 or HeLa epithelial cells with the SCFAs butyrate or propionate at physiological concentrations enhanced NF-κB activation induced by TLR5, TLR2/1, TLR4 and TLR9 agonists. NF-κB activation in response to TNFα was also increased by SCFAs. Comparative transcript analysis of HT-29 colon epithelial cells revealed that SCFAs enhanced TLR5-induced transcription of TNFα but dampened or even abolished the TLR5-mediated induction of IL-8 and monocyte chemotactic protein 1 (MCP-1). SCFAs are known inhibitors of histone deacetylases (HDACs). Butyrate or propionate caused a rapid increase in histone acetylation in epithelial cells, similar to the small molecule HDAC inhibitor Trichostatin A (TSA). TSA also mimicked the effects of SCFAs on TLR-NF-κB responses. This study shows that bacterial SCFAs rapidly alter the epigenetic state of host cells resulting in redirection of the innate immune response and selective reprogramming of cytokine/chemokine expression. |
| first_indexed | 2024-04-13T22:43:53Z |
| format | Article |
| id | doaj.art-93d645fd1dca4afd9a90d9acffc72feb |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T22:43:53Z |
| publishDate | 2015-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-93d645fd1dca4afd9a90d9acffc72feb2022-12-22T02:26:30ZengFrontiers Media S.A.Frontiers in Immunology1664-32242015-11-01610.3389/fimmu.2015.00554160390Redirection of epithelial immune responses by short chain fatty acids through inhibition of histone deacetylasesMay Young eLin0Marcel Robert de Zoete1Jos P.M. van Putten2Karin eStrijbis3Utrecht UniversityUtrecht UniversityUtrecht UniversityUtrecht UniversityShort-Chain Fatty Acids (SCFAs) are products of microbial fermentation that are important for intestinal epithelial health. Here we describe that SCFAs have rapid and reversible effects on Toll-like receptor (TLR) responses in epithelial cells. Incubation of HEK293 or HeLa epithelial cells with the SCFAs butyrate or propionate at physiological concentrations enhanced NF-κB activation induced by TLR5, TLR2/1, TLR4 and TLR9 agonists. NF-κB activation in response to TNFα was also increased by SCFAs. Comparative transcript analysis of HT-29 colon epithelial cells revealed that SCFAs enhanced TLR5-induced transcription of TNFα but dampened or even abolished the TLR5-mediated induction of IL-8 and monocyte chemotactic protein 1 (MCP-1). SCFAs are known inhibitors of histone deacetylases (HDACs). Butyrate or propionate caused a rapid increase in histone acetylation in epithelial cells, similar to the small molecule HDAC inhibitor Trichostatin A (TSA). TSA also mimicked the effects of SCFAs on TLR-NF-κB responses. This study shows that bacterial SCFAs rapidly alter the epigenetic state of host cells resulting in redirection of the innate immune response and selective reprogramming of cytokine/chemokine expression.http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00554/fullFlagellinToll-Like ReceptorsNF-κBhistone acetylationButyrateHDAC |
| spellingShingle | May Young eLin Marcel Robert de Zoete Jos P.M. van Putten Karin eStrijbis Redirection of epithelial immune responses by short chain fatty acids through inhibition of histone deacetylases Frontiers in Immunology Flagellin Toll-Like Receptors NF-κB histone acetylation Butyrate HDAC |
| title | Redirection of epithelial immune responses by short chain fatty acids through inhibition of histone deacetylases |
| title_full | Redirection of epithelial immune responses by short chain fatty acids through inhibition of histone deacetylases |
| title_fullStr | Redirection of epithelial immune responses by short chain fatty acids through inhibition of histone deacetylases |
| title_full_unstemmed | Redirection of epithelial immune responses by short chain fatty acids through inhibition of histone deacetylases |
| title_short | Redirection of epithelial immune responses by short chain fatty acids through inhibition of histone deacetylases |
| title_sort | redirection of epithelial immune responses by short chain fatty acids through inhibition of histone deacetylases |
| topic | Flagellin Toll-Like Receptors NF-κB histone acetylation Butyrate HDAC |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00554/full |
| work_keys_str_mv | AT mayyoungelin redirectionofepithelialimmuneresponsesbyshortchainfattyacidsthroughinhibitionofhistonedeacetylases AT marcelrobertdezoete redirectionofepithelialimmuneresponsesbyshortchainfattyacidsthroughinhibitionofhistonedeacetylases AT jospmvanputten redirectionofepithelialimmuneresponsesbyshortchainfattyacidsthroughinhibitionofhistonedeacetylases AT karinestrijbis redirectionofepithelialimmuneresponsesbyshortchainfattyacidsthroughinhibitionofhistonedeacetylases |