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Upregulation of intestinal mucosal mast cells expressing VPAC1 in close proximity to vasoactive intestinal polypeptide in inflammatory bowel disease and murine colitis
Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.ORCID iD: 0000-0001-8817-6403
Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.ORCID iD: 0000-0001-7518-9213
Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.ORCID iD: 0000-0002-3250-5367
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2019 (English)In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 31, no 3, article id e13503Article in journal (Refereed) Published
Abstract [en]

Background

Mast cells (MCs) and vasoactive intestinal polypeptide (VIP) have been proposed as regulators of the intestinal barrier and inflammation. Our aim was to map the distribution in inflammatory bowel disease (IBD) and murine colitis.

Methods

MCs, VIP, and VIP‐receptors (VPACs) were quantified by immunofluorescence and enzyme‐immunoassay (EIA) in ileal tissues (villus epithelium (VE) and adjacent VE, ie, VE next to the follicle‐associated epithelium, (FAE)) from Crohn's disease (CD; n = 16) and non‐IBD patients, and in colonic specimens of ulcerative colitis (UC; n = 12) and healthy controls (HCs). In addition, VIP levels were measured in plasma from HCs, non‐IBD, and IBD in remission (CD n = 30; UC n = 30). Colon, ileum, and plasma from mice with dextran sulfate sodium (DSS)‐induced colitis and control mice were analyzed likewise.

Key Results

FAE‐adjacent VE in ileum of CD possessed more MCs (P < 0.05) and MCs expressing VPAC1 (P < 0.05), but not VPAC2, compared to controls. Both adjacent and regular VE of CD had more MCs co‐localizing/in close proximity to VIP (P < 0.05). In UC colon, more MCs (P < 0.0005), MCs close to VIP (P < 0.0005), and MCs expressing VPAC1 (P < 0.05) were found compared to controls. VIP levels were elevated in plasma from CD and UC compared to controls (P < 0.0005). Colon of DSS mice showed more MCs and MCs close to VIP (P < 0.05) compared to control mice. In vitro experiments revealed MCs expressing VPACs and internalized VIP after 120 minutes of VIP‐stimulation.

Conclusions and Inferences

Communication between MCs and VIP is upregulated during IBD and mice colitis. In CD patients, the epithelium next to FAE seems to be more involved than the surrounding VE, suggesting increased MC‐VIP‐interactions in this intestinal region.

Place, publisher, year, edition, pages
Wiley-Blackwell Publishing Inc., 2019. Vol. 31, no 3, article id e13503
Keywords [en]
Crohns disease; inflammation; neuro-immune interactions; ulcerative colitis
National Category
Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:liu:diva-154978DOI: 10.1111/nmo.13503ISI: 000459504300019PubMedID: 30407703Scopus ID: 2-s2.0-85056206783OAI: oai:DiVA.org:liu-154978DiVA, id: diva2:1294745
Note

Funding Agencies|Swedish Research Council (VR-Medicine and Health) [2014-02537, 2017-02475]; Swedish Foundation For Strategic Research [RB13-016]; Lions Clubs International Foundation; Mattssons Fastighetsutveckling i Stockholm AB

Available from: 2019-03-08 Created: 2019-03-08 Last updated: 2019-07-05Bibliographically approved

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Casado Bedmar, Maria TeresaHeil, StéphanieMyrelid, PärSöderholm, Johan DKeita, Åsa
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Division of Surgery, Orthopedics and OncologyFaculty of Medicine and Health SciencesDepartment of Surgery in Linköping
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