Effect of the proinflammatory cytokine TNF-α on intestinal riboflavin uptake: inhibition mediated via transcriptional mechanism(s)

American Journal of Physiology. Cell Physiology
Kasin Yadunandam AnandamHamid M Said

Abstract

Riboflavin (RF), is essential for normal cellular metabolism/function. Intestinal RF absorption occurs via a specific carrier-mediated process that involves the apical transporter RFVT-3 ( SLC52A3) and the basolateral RFVT-1 (SLC52A1). Previously, we characterized different cellular/molecular aspects of the intestinal RF uptake process, but nothing is known about the effect of proinflammatory cytokines on the uptake event. We addressed this issue using in vitro, ex vivo, and in vivo models. First, we determined the level of mRNA expression of the human (h)RFVT-3 and hRFVT-1 in intestinal tissue of patients with inflammatory bowel disease (IBD) and observed a markedly lower level compared with controls. In the in vitro model, exposing Caco-2 cells to tumor necrosis factor-α (TNF-α) led to a significant inhibition in RF uptake, an effect that was abrogated upon knocking down TNF receptor 1 (TNFR1). The inhibition in RF uptake was associated with a significant reduction in the expression of hRFVT-3 and -1 protein and mRNA levels, as well as in the activity of the SLC52A3 and SLC52A1 promoters. The latter effects appear to involve Sp1 and NF-κB sites in these promoters. Similarly, exposure of mouse small intestinal enteroids and wi...Continue Reading

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Citations

Dec 10, 2019·American Journal of Physiology. Renal Physiology·Shoujin HaoNicholas R Ferreri
Mar 20, 2020·Journal of Nutrition and Metabolism·Sara Jarmakiewicz-CzajaRafał Filip
Jun 20, 2020·Digestive Diseases and Sciences·Christopher W HeskettVeedamali S Subramanian
Nov 5, 2020·American Journal of Physiology. Gastrointestinal and Liver Physiology·Kasin Yadunandam AnandamHamid M Said

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Methods Mentioned

BETA
protein folding
protein assay
PCR

Software Mentioned

Origene
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COR

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