INVESTIGADORES
ROMANIN David Emmanuel
congresos y reuniones científicas
Título:
Modulation of intestinal epithelial innate response by microbial fermentation products
Autor/es:
IRAPORDA, C; ROMANIN, D; PEREYRA, E; PIGNATARO, O; RUMBO, M; ABRAHAM, AG; GARROTE, G
Lugar:
Mar del Plata
Reunión:
Congreso; LXII Reunión científica anual SAI; 2014
Institución organizadora:
Sociedad Argentina de Inmunología
Resumen:
Short chain fatty
acids (SCFA), acetate, propionate and butyrate are the main fermentation
products of intestinal microbiota. Beyond in
situ generation, they can also be found, as well as lactic acid, in
fermented food products. These molecules have been identified as targets of
G-protein coupled receptors and are putative mediators of host immune response
modulation. The aim of this work was to
analyze the capacity of SCFA to modulate intestinal epithelial innate response.
We used reporter cell line Caco2-CCL20:luc, that is a human intestinal
epithelial line stably transfected with luciferase under the control of CCL20
promoter. We used dose response pretreatment with neutralized filtrated
solutions of acetate, propionate, lactate and butyrate (1 to 100 mM). 30 minutes
pretreatment with the different SCFA downregulated in a dose response manner
the luciferase activity induced by stimulation with either flagellin of S. typhimurium (FliC, 1 µg/ml) or IL-1β (10 ng/ml) as well (p˂0.05). Similar
results were observed at the mRNA level using RTqPCR. Maximal inhibition of
FliC-induced CCL20 expression was observed upon pretretment with 100 mM of SCFA (p˂0.05). In
all cases, butyrate and propionate showed higher capacity to modulate
activation than lactate and acetate. SCFA pretreatment does not affect basal
expression of CCL20, neither of different housekeeping epithelial cell genes. Using
transient transfection with a NFkB driven reporter system we observed that
lactate pretreatment downregulates this signaling pathway in Caco-2 cells. Although
SCFA pretreatment affects intracellular levels of AMPc, we could not observed
inhibition of SCFA activity upon pretreatment of cells with Bordetella pertussis toxin. Our
results showed that SCFA, at concentrations that can be found within the
colonic lumen or in fermented food products can modulate epithelial innate
response in vitro