The role of SP-D in human colonic inflammatory bowel disease and in murine DSS induced colitis

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Background: Inflammatory bowel diseases (IBD) are disorders of the gastrointestinal tract. Surfactant protein D (SP-D) is expressed in the intestinal epithelium and is essential for innate host defence and regulation of inflammatory responses. Genetic variations of SP-D are associated with clinical IBD but SP-D effects in disease development are unknown. We hypothesized that SP-D ameliorates IBD inflammation. Methods: Surgical specimens from IBD patients including Crohn’s disease (CD) (n=9) and ulcerative colitis (UC) (n=18) were scored for expression of SP-D and inflammatory activity. C57BL6 Sftpd+/+ and Sftpd-/- littermate mice were subjected to drinking water (control), 1.5% DSS for 7 days or 1% DSS for 7 days followed by 3 days of water. Weight loss and stool were monitored daily. Colonic levels of inflammatory markers (TNF-α, IFN-γ, CCL-2 and IL-6) were measured by ELISA. H&E-stained tissue was scored for histologic damage. Immunohistochemical stainings were used to quantify the mucosal thickness, epithelial apoptosis, crypt cell proliferation and infiltration of inflammatory cells. Results: Surgical specimens from IBD patients showed a significant positive correlation between immunoscore for SP-D and inflammatory activity (R2 = 0.92, p = <0.0001). DSS induced significant inflammation with weight loss, bloody diarrhoea, increased inflammatory markers and tissue destruction. These changes were unaffected by SP-D genotype/deficiency except for increased TNF-α in sftpd-/- mice during the restitution phase. Conclusion: Although anti-inflammatory effects of SP-D were limited in DSS-induced inflammation in mice, a positive correlation between inflammatory activity and immunoscore for SP-D in IBD patients supports an anti-inflammatory role of SP-D in clinical disease.
Antal sider1
StatusUdgivet - 2017
Begivenhed44th Annual Meeting of the Scandinavian Society of Immunology - Stockholm, Sverige
Varighed: 17. okt. 201720. okt. 2017
Konferencens nummer: 44


Konference44th Annual Meeting of the Scandinavian Society of Immunology