Colonic expression of the peptide transporter PEPT1 is downregulated during intestinal inflammation and is not required for NOD2-dependent immune activation
| Autor: | R. Balfour Sartor, Nicola Schaltenberg, Dirk Haller, Matthias Prager, Tilo Wuensch, Sina S Ullrich, Eva Rath, Peter Bugert, Hannelore Daniel, Mathias Chamaillard, Stephan Schulz, Ulf B. Goebel, Heiko Witt, Carsten Büning |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Adolescent Genotype medicine.medical_treatment Nod2 Signaling Adaptor Protein Down-Regulation Inflammation Inflammatory bowel disease Peptide Transporter 1 Polymorphism Single Nucleotide Descending colon Tissue Culture Techniques Mice Young Adult Crohn Disease NOD2 medicine Immunology and Allergy Animals Humans Ileitis RNA Messenger Colitis Immunity Mucosal Aged Symporters business.industry Dextran Sulfate Gastroenterology Middle Aged medicine.disease digestive system diseases Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Cytokine Trinitrobenzenesulfonic Acid Gene Knockdown Techniques Immunology Cytokines Tumor necrosis factor alpha Colitis Ulcerative Female medicine.symptom business Acetylmuramyl-Alanyl-Isoglutamine |
| Zdroj: | Inflammatory bowel diseases. 20(4) |
| ISSN: | 1536-4844 |
| Popis: | PEPT1 was proposed to be expressed only in inflamed colonic tissues in which it could contribute to inflammatory bowel disease (IBD) development by transporting bacterial peptides, such as muramyl dipeptide (MDP), that activate intracellular pattern recognition receptors, such as the nucleotide-binding and oligomerization domain 2. To better define the pathological relevance of this transporter, we analyzed PEPT1 expression during intestinal inflammation and studied the susceptibility of Pept1-deficient (Pept1) mice to experimental colitis.Wild-type and Pept1 mice were treated with dextran sulfate sodium and 2,4,6-trinitrobenzene sulfonic acid to induce colitis, and MDP-induced cytokine expression was studied in colonic tissue cultures. PEPT1 expression was characterized in mouse models of Crohn's disease-like ileitis (Tnf) or colitis (Il-10, Il-10XTlr2) and endoscopic tissue samples from descending colon of patients with IBD (n = 11) and controls (n = 17). Moreover, the prevalence of the PEPT1 single-nucleotide polymorphism rs2297322 was tested in German patients with IBD (n = 458) and controls (n = 452).PEPT1 expression was consistently reduced under condition of acute or chronic experimental inflammation. Wild-type and Pept1 mice revealed comparable susceptibility to dextran sulfate sodium-induced and 2,4,6-trinitrobenzene sulfonic acid-induced colitis, and MDP-induced cytokine expression was PEPT1-independent. PEPT1 expression levels were also decreased in descending colon of patients with IBD during acute inflammation, but the rs2297322 single-nucleotide polymorphism was not associated with IBD susceptibility in the German cohort.PEPT1 expression is reduced during intestinal inflammation and PEPT1 is neither required for MDP-induced immune response nor is the PEPT1 rs2297322 single-nucleotide polymorphism associated with IBD susceptibility in our German cohort. These data strongly argue against a primary role of PEPT1 in the initiation or progression of IBD. |
| Databáze: | OpenAIRE |
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