TY - JOUR
T1 - Salmonella Typhimurium Infection Reduces the Ascorbic Acid Uptake in the Intestine
AU - Teafatiller, Trevor
AU - Subramanya, Sandeep B.
AU - Lambrecht, Nils
AU - Subramanian, Veedamali S.
N1 - Funding Information:
The current study was supported by the National Institutes of Health (NIH) grant DK107474.
Publisher Copyright:
© 2023 Trevor Teafatiller et al.
PY - 2023
Y1 - 2023
N2 - Salmonella Typhimurium infection of the gastrointestinal tract leads to damage that compromises the integrity of the intestinal epithelium and results in enterocolitis and inflammation. Salmonella infection promotes the expression of inflammasome NLRP3, leading to activation and release of proinflammatory cytokines such as IL-1β, and the infected host often displays altered nutrient levels. To date, the effect of Salmonella infection and proinflammatory cytokine IL-1β on the intestinal uptake of ascorbic acid (AA) is unknown. Our results revealed a marked decrease in the rate of AA uptake in mouse jejunum infected with Salmonella wild type (WT). However, the nonpathogenic mutant (Δ invA Δ spiB) strain did not affect AA uptake. The decrease in AA uptake due to Salmonella WT infection is accompanied by significantly lower expression of mouse (m)SVCT1 protein, mRNA, and hnRNA levels. NLRP3 and IL-1β expression levels were markedly increased in Salmonella-infected mouse jejunum. IL-1β-exposed Caco-2 cells displayed marked inhibition in AA uptake and significantly decreased hSVCT1 expression at both protein and mRNA levels. Furthermore, the activity of the SLC23A1 promoter was significantly inhibited by IL-1β exposure. In addition, GRHPR (a known SVCT1 interactor) protein and mRNA expression levels were significantly reduced in Salmonella-infected mouse jejunum. These results indicate that Salmonella infection inhibits AA absorption in mouse jejunum and IL-1β-exposed Caco-2 cells. The observed inhibitory effect may partially be mediated through transcriptional mechanisms.
AB - Salmonella Typhimurium infection of the gastrointestinal tract leads to damage that compromises the integrity of the intestinal epithelium and results in enterocolitis and inflammation. Salmonella infection promotes the expression of inflammasome NLRP3, leading to activation and release of proinflammatory cytokines such as IL-1β, and the infected host often displays altered nutrient levels. To date, the effect of Salmonella infection and proinflammatory cytokine IL-1β on the intestinal uptake of ascorbic acid (AA) is unknown. Our results revealed a marked decrease in the rate of AA uptake in mouse jejunum infected with Salmonella wild type (WT). However, the nonpathogenic mutant (Δ invA Δ spiB) strain did not affect AA uptake. The decrease in AA uptake due to Salmonella WT infection is accompanied by significantly lower expression of mouse (m)SVCT1 protein, mRNA, and hnRNA levels. NLRP3 and IL-1β expression levels were markedly increased in Salmonella-infected mouse jejunum. IL-1β-exposed Caco-2 cells displayed marked inhibition in AA uptake and significantly decreased hSVCT1 expression at both protein and mRNA levels. Furthermore, the activity of the SLC23A1 promoter was significantly inhibited by IL-1β exposure. In addition, GRHPR (a known SVCT1 interactor) protein and mRNA expression levels were significantly reduced in Salmonella-infected mouse jejunum. These results indicate that Salmonella infection inhibits AA absorption in mouse jejunum and IL-1β-exposed Caco-2 cells. The observed inhibitory effect may partially be mediated through transcriptional mechanisms.
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U2 - 10.1155/2023/2629262
DO - 10.1155/2023/2629262
M3 - Article
C2 - 36704315
AN - SCOPUS:85146957765
SN - 0962-9351
VL - 2023
JO - Mediators of Inflammation
JF - Mediators of Inflammation
M1 - 2629262
ER -