ArticlePflugers Archiv : European journal of physiology2006
Tumor necrosis factor-alpha and interferon-gamma increase PepT1 expression and activity in the human colon carcinoma cell line Caco-2/bbe and in mouse intestine.
Article in Pflugers Archiv : European journal of physiology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 51 citations in OpenAlex.
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- Gastrointestinal dynamics, immune response, and nutrient digestibility of weanling pigs fed diets supplemented with enzymatically treated yeast1.Journal of animal science · 2022Article
- Tumor necrosis factor α impedes colonic thiamin pyrophosphate and free thiamin uptake: involvement of JNK/ERKAmerican journal of physiology. Cell physiology · 2022Article
- Reduced active transcellular intestinal oxalate secretion contributes to the pathogenesis of obesity-associated hyperoxaluria.Kidney international · 2018Article
- Function, Regulation, and Pathophysiological Relevance of the POT Superfamily, Specifically PepT1 in Inflammatory Bowel Disease.Comprehensive Physiology · 2018Review
- Dormant cancer cells accumulate high protoporphyrin IX levels and are sensitive to 5-aminolevulinic acid-based photodynamic therapy.Scientific reports · 2016Article
- Salmonella infection inhibits intestinal biotin transport: cellular and molecular mechanisms.American journal of physiology. Gastrointestinal and liver physiology · 2015Article
- Epithelial transport in inflammatory bowel diseases.Inflammatory bowel diseases · 2014Review
- The role and pathophysiological relevance of membrane transporter PepT1 in intestinal inflammation and inflammatory bowel disease.American journal of physiology. Gastrointestinal and liver physiology · 2012Review
- Cytokine regulation of OCTN2 expression and activity in small and large intestine.Inflammatory bowel diseases · 2011Article
- Evidence for intestinal heterogenic expression of di-tripeptides transporter PepT1 during experimental cryptosporidiosis in neonatal rats.Parasitology research · 2009Article
- Malnutrition as an enteric infectious disease with long-term effects on child development.Nutrition reviews · 2008Review
- Regulation of the oligopeptide transporter, PEPT-1, in DSS-induced rat colitis.Digestive diseases and sciences · 2007Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
A major mechanism for apical peptide absorption by small intestine is via the proton-coupled transporter PepT1. PepT1 is expressed at a high level in proximal small intestine, but it is not expressed in the healthy colon. However, in chronic states of intestinal inflammation, such as in Crohn's disease and ulcerative colitis, PepT1 expression in colonic epithelia is increased, serving as a pathway for entry of bacteria-derived molecules such as muramyl dipeptide (MDP) and fMet-Leu-Phe (fMLP). As little is known of how inflammation induces PepT1, we investigated whether or not inflammatory cytokines and mediators such as interleukins (IL)-1beta, IL-2, IL-8, IL-10, tumor necrosis factor-alpha, (TNF-alpha) and interferon-gamma (IFN-gamma ) up-regulate PepT1 activity and expression. Uptake of the PepT1 substrate glycylsarcosine [(3)H]-Gly-Sar was studied in vitro in the human colon carcinoma cell line Caco2/bbe monolayers as well as in vivo in mice injected with cytokines. TNF-alpha and IFN-gamma increased the activity, and total and apical membrane protein expression of PepT1 protein in a concentration- and time-dependent fashion. No changes in PepT1 mRNA were observed, suggesting post-transcriptional regulation. All three cytokines increased PepT1 protein expression in mouse proximal and distal colon but not in jejunum or ileum. TNF-alpha and IFN-gamma, but not IL-1beta, increased Gly-Sar uptake in mouse proximal and distal colon; however, no changes were observed in the small intestine with any cytokine treatment. Whereas neither TNF-alpha nor IFN-gamma increased PepT1 mRNA expression in any segment of the intestine, treatment with IL-1beta increased PepT1 mRNA expression in mouse proximal and distal colon and decreased PepT1 mRNA expression in jejunum and ileum. Since PepT1 transports bacteria-derived peptides, the up-regulation of protein expression and activity observed after treatment with TNF-alpha or IFN-gamma may play a role in activating host responses in involved colon.
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