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• W2930733657 abstract "Thiamin (vitamin B 1 ) is essential for normal cellular metabolism and function. Pancreatic acinar cells (PACs) obtain thiamin from the circulation via a specific carrier-mediated process that involves the plasma membrane thiamin transporters 1 and 2 (THTR-1 and THTR-2; products of SLC19A2 and SLC19A3 genes, respectively). There is nothing known about the effect of bacterial products/toxins on thiamin uptake by PACs. We addressed this issue in the present investigation by examining the effect of bacterial flagellin on physiological and molecular parameters of thiamin uptake by PACs. We used human primary PACs, mice in vivo, and cultured mouse-derived pancreatic acinar 266-6 cells in our investigation. The results showed that exposure of human primary PACs to flagellin led to a significant inhibition in thiamin uptake; this inhibition was associated with a significant decrease in expression of THTR-1 and -2 at the protein and mRNA levels. These findings were confirmed in mice in vivo as well as in cultured 266-6 cells. Subsequent studies showed that flagellin exposure markedly suppressed the activity of the SLC19A2 and SLC19A3 promoters and that this effect involved the Sp1 regulatory factor. Finally, knocking down Toll-like receptor 5 by use of gene-specific siRNA was found to lead to abrogation in the inhibitory effect of flagellin on PAC thiamin uptake. These results show, for the first time, that exposure of PACs to flagellin negatively impacts the physiological and molecular parameters of thiamin uptake and that this effect is mediated at the level of transcription of the SLC19A2 and SLC19A3 genes. NEW & NOTEWORTHY The present study demonstrates, for the first time, that prolonged exposure of pancreatic acinar cells to flagellin inhibits uptake of vitamin B 1 , a micronutrient that is essential for energy metabolism and ATP production. This effect is mediated at the level of transcription of the SLC19A2 and SLC19A3 genes and involves the Sp1 transcription factor." @default.
• W2930733657 created "2019-04-11" @default.
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• W2930733657 date "2019-06-01" @default.
• W2930733657 modified "2023-10-12" @default.
• W2930733657 title "Effect of bacterial flagellin on thiamin uptake by human and mouse pancreatic acinar cells: inhibition mediated at the level of transcription of thiamin transporters 1 and 2" @default.
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• W2930733657 doi "https://doi.org/10.1152/ajpgi.00048.2019" @default.
• W2930733657 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6620585" @default.
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