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

• Published in: Biology open Vol. 7; no. 7; p. bio034140
• Main Authors: Khandagale, Avinash, Kittner, Jens M, Mann, Amrit, Ascher, Stefanie, Kollar, Bettina, Reinhardt, Christoph
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Ltd 2018; The Company of Biologists
• Subjects: Bleeding; Body weight loss; Coagulation; Coagulation factor IX; Coagulation factors; Colitis; Colon; Dextran; Dextran sulfate; Dextrans; Disorders; Epithelial cells; Epithelium; Factor IX deficiency; Hemophilia; Hemophilia B; Immune system; Infiltration; Inflammatory bowel disease; Inflammatory bowel diseases; Intestine; Leukocytes (neutrophilic); Lipopolysaccharides; Macrophages; Medicin och hälsovetenskap; Mice; Microbiota; Patients; Peroxidase; Proteins; Rodents; Small intestine; Sodium; Sulfates; Thromboembolism; Toll-like receptor-2; Toll-like receptors; Weight loss; Weight reduction; Toll-like receptor-2; Coagulation factor IX; Hemophilia B; Microbiota; Colitis
• ISSN: 2046-6390; 2046-6390
• DOI: 10.1242/bio.034140

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 -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, -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 -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 -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.