Coagulation factor 9-deficient mice are protected against dextran sulfate sodium-induced colitis

Autor: Avinash Khandagale, Jens M. Kittner, Amrit Mann, Stefanie Ascher, Bettina Kollar, Christoph Reinhardt
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Biology Open, Vol 7, Iss 7 (2018)
Druh dokumentu: article
ISSN: 2046-6390
DOI: 10.1242/bio.034140
Popis: Patients with inflammatory bowel disease (IBD) are susceptible to thromboembolism. Interestingly, IBD occurs less frequently in patients with inherited bleeding disorders. Therefore, we analyzed whether F9-deficiency is protective against the onset of acute colitis in a genetic hemophilia B mouse model. In the 3.5% dextran sulfate sodium (DSS)-induced colitis model, F9-deficient mice were protected from body-weight loss and had a reduced disease activity score. We detected decreased colonic myeloperoxidase activity and decreased CXCL1 levels in DSS-treated F9-deficient mice compared with wild-type (WT) littermate controls, indicating decreased neutrophil infiltration. Remarkably, we identified expression of coagulation factor IX (FIX) protein in small intestinal epithelial cells (MODE-K). In epithelial cell cultures, cellular FIX protein expression was increased following stimulation with the bacterial Toll-like receptor agonists lipopolysaccharide, macrophage-activating lipopeptide-2 and Pam3CSK4. Thus, we revealed a protective role of F9-deficiency in DSS-induced colitis and identified the intestinal epithelium as a site of ectopic FIX. This article has an associated First Person interview with the first author of the paper.
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