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Intestinal inflammation and prolonged infection are associated with increased serum and intestinal mucosa levels of tumor necrosis factor-\u03b1 (TNF-\u03b1), which also exerts profound effects on the intestinal absorption process. Elevated levels of TNF-\u03b1 have been linked to the pathogenesis of inflammatory bowel disease (IBD) and malabsorption of nutrients, and patients with this condition have low levels of vitamin C. To date, little is known about the effect of TNF-\u03b1 on intestinal absorption of vitamin C. We studied the impact of TNF-\u03b1 on ascorbic acid (AA) transport using a variety of intestinal preparations. The expression level of human SVCT-1 mRNA is significantly lower in patients with IBD. TNF-\u03b1 treated Caco-2 cells and mice showed a significant inhibition of intestinal<jats:sup>14<\/jats:sup>C-AA uptake. This inhibition was associated with significant decreases in SVCT-1 protein, mRNA, and heterogeneous nuclear RNA levels in TNF-\u03b1 treated Caco-2 cells, mouse jejunum, and enteroids. Also, TNF-\u03b1 caused a significant inhibition in the SLC23A1 promoter activity. Furthermore, treatment of Caco-2 cells with celastrol (NF-\u03baB inhibitor) blocked the inhibitory effect caused by TNF-\u03b1 on AA uptake, SVCT-1 protein, and mRNA expression, as well as the activity of SLC23A1 promoter. Treatment of TNF-\u03b1 also led to a significant decrease in the expression of hepatocyte nuclear factor-1-\u03b1, which drives the basal activity of SLC23A1 promoter, and this effect was reversed by celastrol. Together, these findings show that TNF-\u03b1 inhibits intestinal AA uptake, and this effect is mediated, at least in part, at the level of transcription of the SLC23A1 gene via the NF-\u03baB pathway.<\/jats:p><jats:p>NEW &amp; NOTEWORTHY Our findings show that tumor necrosis factor-\u03b1 inhibits intestinal ascorbic acid uptake in both in vitro and in vivo systems, and this inhibitory effect is mediated, at least in part, at the level of transcription of the SLC23A1 (sodium-dependent vitamin C transporter-1) gene via the NF-\u03baB pathway.<\/jats:p>","DOI":"10.1152\/ajpgi.00071.2018","type":"journal-article","created":{"date-parts":[[2018,4,6]],"date-time":"2018-04-06T19:44:14Z","timestamp":1523043854000},"page":"G241-G248","source":"Crossref","is-referenced-by-count":51,"title":["Tumor necrosis factor alpha reduces intestinal vitamin C uptake: a role for NF-\u03baB-mediated signaling"],"prefix":"10.1152","volume":"315","author":[{"given":"Veedamali 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