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

Anders Bathum Nexøe, Bartosz Pilecki, Sebastian Leicht von Huth, Jesper Bonnet Møller, Steffen Husby, Andreas Arnholdt Pedersen, Sönke Detlefsen, Niels Marcussen, Uffe Holmskov, Grith Lykke Sørensen

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Abstrakt

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.
OriginalsprogEngelsk
Publikationsdato2017
Antal sider1
StatusUdgivet - 2017
Begivenhed44th Annual Meeting of the Scandinavian Society of Immunology - Stockholm, Sverige
Varighed: 17. okt. 201720. okt. 2017
Konferencens nummer: 44

Konference

Konference44th Annual Meeting of the Scandinavian Society of Immunology
Nummer44
Land/OmrådeSverige
ByStockholm
Periode17/10/201720/10/2017

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