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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.


Documento: Artículo
Título:Lactate and short chain fatty acids produced by microbial fermentation downregulate proinflammatory responses in intestinal epithelial cells and myeloid cells
Autor:Iraporda, C.; Errea, A.; Romanin, D.E.; Cayet, D.; Pereyra, E.; Pignataro, O.; Sirard, J.C.; Garrote, G.L.; Abraham, A.G.; Rumbo, M.
Filiación:Centro de Investigacion y Desarrollo en Criotecnología de Alimentos (CIDCA, UNLP-CONICET), Calle 47 y 116, La Plata, 1900, Argentina
Instituto de Estudios Inmunológicos y Fisopatológicos (IIFP, UNLP-CONICET), Calle 47 y 115, La Plata, 1900, Argentina
Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, Lille, F-59000, France
Institut National de la Santé et de la Recherche Médicale, U1019, Lille, F-59000, France
Centre National de la Recherche Scientifique, UMR 8204, Lille, F-59000, France
Université Lille Nord de France, Lille, F-59000, France
Instituto de Biología y Medicina Experimental (IBYME, CONICET), Vuelta de Obligado 2490, CABA, Bs. As., 1428, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales (FCEyN, UBA), Argentina
Área Bioquímica y Control de Alimentos, Facultad de Ciencias Exactas, UNLP, Calle 47 y 115, La Plata, 1900, Argentina
Palabras clave: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
Página de inicio:1161
Página de fin:1169
Título revista:Immunobiology
CAS:acetic acid, 127-08-2, 127-09-3, 64-19-7, 71-50-1; butyric acid, 107-92-6, 156-54-7, 461-55-2; cyclic AMP, 60-92-4; interleukin 8, 114308-91-7; lactic acid, 113-21-3, 50-21-5; macrophage inflammatory protein 3alpha, 177404-38-5; propionic acid, 72-03-7, 79-09-4; toll like receptor 4, 203811-83-0; Antigens, CD40; Fatty Acids; Lactic Acid; Tlr4 protein, mouse; Toll-Like Receptor 4; Toll-Like Receptor 5


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---------- APA ----------
Iraporda, C., Errea, A., Romanin, D.E., Cayet, D., Pereyra, E., Pignataro, O., Sirard, J.C.,..., Rumbo, M. (2015) . Lactate and short chain fatty acids produced by microbial fermentation downregulate proinflammatory responses in intestinal epithelial cells and myeloid cells. Immunobiology, 220(10), 1161-1169.
---------- CHICAGO ----------
Iraporda, C., Errea, A., Romanin, D.E., Cayet, D., Pereyra, E., Pignataro, O., et al. "Lactate and short chain fatty acids produced by microbial fermentation downregulate proinflammatory responses in intestinal epithelial cells and myeloid cells" . Immunobiology 220, no. 10 (2015) : 1161-1169.
---------- MLA ----------
Iraporda, C., Errea, A., Romanin, D.E., Cayet, D., Pereyra, E., Pignataro, O., et al. "Lactate and short chain fatty acids produced by microbial fermentation downregulate proinflammatory responses in intestinal epithelial cells and myeloid cells" . Immunobiology, vol. 220, no. 10, 2015, pp. 1161-1169.
---------- VANCOUVER ----------
Iraporda, C., Errea, A., Romanin, D.E., Cayet, D., Pereyra, E., Pignataro, O., et al. Lactate and short chain fatty acids produced by microbial fermentation downregulate proinflammatory responses in intestinal epithelial cells and myeloid cells. 2015;220(10):1161-1169.