Effect of bacterial flagellin on thiamin uptake by human and mouse pancreatic acinar cells: Inhibition mediated at the level of transcription of THTR-1 and 2.

Effect of bacterial flagellin on thiamin uptake by human and mouse pancreatic acinar cells: Inhibition mediated at the level of transcription of THTR-1 and 2. Am J Physiol Gastrointest Liver Physiol. 2019 Mar 28;: Authors: Srinivasan P, Anandam KY, Ramesh V, Geltz ET, Said HM Abstract Thiamin (vitamin B1) is essential for normal cellular metabolism and function. Pancreatic acinar cells (PACs) obtain thiamin from 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 current investigation by examining the effect of the bacterial flagellin on physiological and molecular parameters of the 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 to lead 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 suppresses the activity of the SLC19A2 and SLC19A3 promoters, and that...
Source: Am J Physiol Gastroi... - Category: Gastroenterology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research