ABSTRACT
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.
Footnotes
Competing interests
The authors declare no competing or financial interests.
Author contributions
Conceptualization: C.R.; Validation: A.K., C.R.; Formal analysis: A.K., B.K., C.R.; Investigation: A.K., C.R.; Data curation: A.M., S.A., B.K., C.R.; Writing - original draft: C.R.; Writing - review & editing: A.K., J.M.K., A.M., S.A., B.K., C.R.; Visualization: B.K., C.R.; Supervision: C.R.; Project administration: C.R.; Funding acquisition: C.R.
Funding
The project was funded by the CTH Junior Group Translational Research in Thrombosis and Hemostasis [BMBF 01EO1003 and 01EO1503, TRP X14], DFG Individual Grants [3450/3-1; 3450/5-2] and a project grant from the Boehringer Ingelheim Foundation to C.R.
- Received March 13, 2018.
- Accepted June 20, 2018.
- © 2018. Published by The Company of Biologists Ltd
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
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