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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
Author(s) -
CasadoBedmar Maite,
Heil Stéphanie D. S.,
Myrelid Pär,
Söderholm Johan D.,
Keita Åsa V.
Publication year - 2019
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.13503
Subject(s) - vasoactive intestinal peptide , inflammatory bowel disease , ulcerative colitis , ileum , medicine , colitis , gastroenterology , endocrinology , immunology , receptor , disease , neuropeptide
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.