Lactate and short chain fatty acids produced by microbial fermentation downregulate proinflammatory responses in intestinal epithelial cells and myeloid cells
The use of short chain fatty acids to modulate gastrointestinal inflammatory conditions such as ulcerative colitis has produced encouraging results either in animal models or also in clinical trials. Identifying the key cellular and molecular targets of this activity will contribute to establish the...
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2015
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paper:paper_01712985_v220_n10_p1161_Iraporda2023-06-08T15:18:38Z Lactate and short chain fatty acids produced by microbial fermentation downregulate proinflammatory responses in intestinal epithelial cells and myeloid cells Pereyra, Elba Nora Pignataro, Omar Pedro Immunomodulation Inflammation Innate immunity Lactate Short chain fatty acids acetic acid beta actin butyric acid CD40 antigen cyclic AMP G protein coupled receptor interleukin 12p40 interleukin 6 interleukin 8 intestinal trefoil factor lactic acid macrophage inflammatory protein 3alpha propionic acid short chain fatty acid toll like receptor 4 toll like receptor 5 CD40 antigen fatty acid lactic acid Tlr4 protein, mouse toll like receptor 4 toll like receptor 5 animal cell antiinflammatory activity Article bone marrow cell bone marrow derived dendritic cell bone marrow derived macrophage cell activation concentration response controlled study cytokine production cytokine release down regulation female fermentation gastrointestinal tract human human cell in vitro study inflammation inflammatory bowel disease innate immunity intestine epithelium cell large intestine mouse nonhuman priority journal signal transduction upregulation animal bacterium CACO 2 cell line epithelium cell immunology intestine mucosa microbiology Animals Antigens, CD40 Bacteria Caco-2 Cells Down-Regulation Epithelial Cells Fatty Acids Female Humans Intestinal Mucosa Lactic Acid Mice Myeloid Cells Toll-Like Receptor 4 Toll-Like Receptor 5 The use of short chain fatty acids to modulate gastrointestinal inflammatory conditions such as ulcerative colitis has produced encouraging results either in animal models or also in clinical trials. Identifying the key cellular and molecular targets of this activity will contribute to establish the appropriate combinations/targeting strategies to maximize the efficacy of anti-inflammatory interventions. In the present work, we evaluated in vitro the interaction of lactate, acetate, propionate and butyrate on cells relevant for innate immune response of the gastrointestinal tract. All molecules tested regulate the production of proinflammatory cytokines by TLR-4 and TLR-5 activated intestinal epithelial cells in a dose response manner. Furthermore SCFAs and lactate modulate cytokine secretion of TLR-activated bone marrow derived macrophages and also TLR-dependent CD40 upregulation in bone marrow derived dendritic in a dose-dependent manner. Butyrate and propionate have been effective at concentrations of 1 to 5mM whereas acetate and lactate produced modulatory effects at concentrations higher than 20-50mM in different assays. Our results indicate that in concentrations similar to found in large bowel lumen, all SCFAs tested and lactate can modulate activity of relevant sentinel cell types activated by TLR signals. Modulatory activity was not inhibited by pertussis toxin treatment indicating that the effects are not related to Gi signaling. The use of these molecules in combined or separately as intervention strategy in conditions where epithelial or myeloid cells are main triggers of the inflammatory situation seems appropriate. © 2015 Elsevier GmbH. Fil:Pereyra, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Pignataro, O. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2015 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01712985_v220_n10_p1161_Iraporda http://hdl.handle.net/20.500.12110/paper_01712985_v220_n10_p1161_Iraporda |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Immunomodulation Inflammation Innate immunity Lactate Short chain fatty acids acetic acid beta actin butyric acid CD40 antigen cyclic AMP G protein coupled receptor interleukin 12p40 interleukin 6 interleukin 8 intestinal trefoil factor lactic acid macrophage inflammatory protein 3alpha propionic acid short chain fatty acid toll like receptor 4 toll like receptor 5 CD40 antigen fatty acid lactic acid Tlr4 protein, mouse toll like receptor 4 toll like receptor 5 animal cell antiinflammatory activity Article bone marrow cell bone marrow derived dendritic cell bone marrow derived macrophage cell activation concentration response controlled study cytokine production cytokine release down regulation female fermentation gastrointestinal tract human human cell in vitro study inflammation inflammatory bowel disease innate immunity intestine epithelium cell large intestine mouse nonhuman priority journal signal transduction upregulation animal bacterium CACO 2 cell line epithelium cell immunology intestine mucosa microbiology Animals Antigens, CD40 Bacteria Caco-2 Cells Down-Regulation Epithelial Cells Fatty Acids Female Humans Intestinal Mucosa Lactic Acid Mice Myeloid Cells Toll-Like Receptor 4 Toll-Like Receptor 5 |
| spellingShingle |
Immunomodulation Inflammation Innate immunity Lactate Short chain fatty acids acetic acid beta actin butyric acid CD40 antigen cyclic AMP G protein coupled receptor interleukin 12p40 interleukin 6 interleukin 8 intestinal trefoil factor lactic acid macrophage inflammatory protein 3alpha propionic acid short chain fatty acid toll like receptor 4 toll like receptor 5 CD40 antigen fatty acid lactic acid Tlr4 protein, mouse toll like receptor 4 toll like receptor 5 animal cell antiinflammatory activity Article bone marrow cell bone marrow derived dendritic cell bone marrow derived macrophage cell activation concentration response controlled study cytokine production cytokine release down regulation female fermentation gastrointestinal tract human human cell in vitro study inflammation inflammatory bowel disease innate immunity intestine epithelium cell large intestine mouse nonhuman priority journal signal transduction upregulation animal bacterium CACO 2 cell line epithelium cell immunology intestine mucosa microbiology Animals Antigens, CD40 Bacteria Caco-2 Cells Down-Regulation Epithelial Cells Fatty Acids Female Humans Intestinal Mucosa Lactic Acid Mice Myeloid Cells Toll-Like Receptor 4 Toll-Like Receptor 5 Pereyra, Elba Nora Pignataro, Omar Pedro Lactate and short chain fatty acids produced by microbial fermentation downregulate proinflammatory responses in intestinal epithelial cells and myeloid cells |
| topic_facet |
Immunomodulation Inflammation Innate immunity Lactate Short chain fatty acids acetic acid beta actin butyric acid CD40 antigen cyclic AMP G protein coupled receptor interleukin 12p40 interleukin 6 interleukin 8 intestinal trefoil factor lactic acid macrophage inflammatory protein 3alpha propionic acid short chain fatty acid toll like receptor 4 toll like receptor 5 CD40 antigen fatty acid lactic acid Tlr4 protein, mouse toll like receptor 4 toll like receptor 5 animal cell antiinflammatory activity Article bone marrow cell bone marrow derived dendritic cell bone marrow derived macrophage cell activation concentration response controlled study cytokine production cytokine release down regulation female fermentation gastrointestinal tract human human cell in vitro study inflammation inflammatory bowel disease innate immunity intestine epithelium cell large intestine mouse nonhuman priority journal signal transduction upregulation animal bacterium CACO 2 cell line epithelium cell immunology intestine mucosa microbiology Animals Antigens, CD40 Bacteria Caco-2 Cells Down-Regulation Epithelial Cells Fatty Acids Female Humans Intestinal Mucosa Lactic Acid Mice Myeloid Cells Toll-Like Receptor 4 Toll-Like Receptor 5 |
| description |
The use of short chain fatty acids to modulate gastrointestinal inflammatory conditions such as ulcerative colitis has produced encouraging results either in animal models or also in clinical trials. Identifying the key cellular and molecular targets of this activity will contribute to establish the appropriate combinations/targeting strategies to maximize the efficacy of anti-inflammatory interventions. In the present work, we evaluated in vitro the interaction of lactate, acetate, propionate and butyrate on cells relevant for innate immune response of the gastrointestinal tract. All molecules tested regulate the production of proinflammatory cytokines by TLR-4 and TLR-5 activated intestinal epithelial cells in a dose response manner. Furthermore SCFAs and lactate modulate cytokine secretion of TLR-activated bone marrow derived macrophages and also TLR-dependent CD40 upregulation in bone marrow derived dendritic in a dose-dependent manner. Butyrate and propionate have been effective at concentrations of 1 to 5mM whereas acetate and lactate produced modulatory effects at concentrations higher than 20-50mM in different assays. Our results indicate that in concentrations similar to found in large bowel lumen, all SCFAs tested and lactate can modulate activity of relevant sentinel cell types activated by TLR signals. Modulatory activity was not inhibited by pertussis toxin treatment indicating that the effects are not related to Gi signaling. The use of these molecules in combined or separately as intervention strategy in conditions where epithelial or myeloid cells are main triggers of the inflammatory situation seems appropriate. © 2015 Elsevier GmbH. |
| author |
Pereyra, Elba Nora Pignataro, Omar Pedro |
| author_facet |
Pereyra, Elba Nora Pignataro, Omar Pedro |
| author_sort |
Pereyra, Elba Nora |
| title |
Lactate and short chain fatty acids produced by microbial fermentation downregulate proinflammatory responses in intestinal epithelial cells and myeloid cells |
| title_short |
Lactate and short chain fatty acids produced by microbial fermentation downregulate proinflammatory responses in intestinal epithelial cells and myeloid cells |
| title_full |
Lactate and short chain fatty acids produced by microbial fermentation downregulate proinflammatory responses in intestinal epithelial cells and myeloid cells |
| title_fullStr |
Lactate and short chain fatty acids produced by microbial fermentation downregulate proinflammatory responses in intestinal epithelial cells and myeloid cells |
| title_full_unstemmed |
Lactate and short chain fatty acids produced by microbial fermentation downregulate proinflammatory responses in intestinal epithelial cells and myeloid cells |
| title_sort |
lactate and short chain fatty acids produced by microbial fermentation downregulate proinflammatory responses in intestinal epithelial cells and myeloid cells |
| publishDate |
2015 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01712985_v220_n10_p1161_Iraporda http://hdl.handle.net/20.500.12110/paper_01712985_v220_n10_p1161_Iraporda |
| work_keys_str_mv |
AT pereyraelbanora lactateandshortchainfattyacidsproducedbymicrobialfermentationdownregulateproinflammatoryresponsesinintestinalepithelialcellsandmyeloidcells AT pignataroomarpedro lactateandshortchainfattyacidsproducedbymicrobialfermentationdownregulateproinflammatoryresponsesinintestinalepithelialcellsandmyeloidcells |
| _version_ |
1768544907152064512 |