PMID- 30407703 OWN - NLM STAT- MEDLINE DCOM- 20200122 LR - 20200122 IS - 1365-2982 (Electronic) IS - 1350-1925 (Linking) VI - 31 IP - 3 DP - 2019 Mar TI - Upregulation of intestinal mucosal mast cells expressing VPAC1 in close proximity to vasoactive intestinal polypeptide in inflammatory bowel disease and murine colitis. PG - e13503 LID - 10.1111/nmo.13503 [doi] AB - 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. CI - (c) 2018 John Wiley & Sons Ltd. FAU - Casado-Bedmar, Maite AU - Casado-Bedmar M AD - Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics & Oncology, Linkoping University, Linkoping, Sweden. FAU - Heil, Stephanie D S AU - Heil SDS AD - Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics & Oncology, Linkoping University, Linkoping, Sweden. FAU - Myrelid, Par AU - Myrelid P AD - Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics & Oncology, Linkoping University, Linkoping, Sweden. AD - Department of Surgery, County Council of Ostergotland, Linkoping, Sweden. FAU - Soderholm, Johan D AU - Soderholm JD AD - Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics & Oncology, Linkoping University, Linkoping, Sweden. AD - Department of Surgery, County Council of Ostergotland, Linkoping, Sweden. FAU - Keita, Asa V AU - Keita AV AUID- ORCID: 0000-0002-6820-0215 AD - Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics & Oncology, Linkoping University, Linkoping, Sweden. LA - eng GR - 2014-02537/Swedish Research Council/International GR - 2017-02475/Swedish Research Council/International GR - RB13-016/Swedish Foundation for Strategic Research/International GR - Lions Clubs International Foundation/International GR - Mattssons Fastighetsutveckling i Stockholm AB/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181108 PL - England TA - Neurogastroenterol Motil JT - Neurogastroenterology and motility JID - 9432572 RN - 0 (Receptors, Vasoactive Intestinal Polypeptide, Type I) RN - 0 (VIPR1 protein, human) RN - 0 (Vipr1 protein, mouse) RN - 37221-79-7 (Vasoactive Intestinal Peptide) RN - 9042-14-2 (Dextran Sulfate) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Animals MH - Cell Count MH - Colitis, Ulcerative/chemically induced/*metabolism MH - Crohn Disease/metabolism MH - Dextran Sulfate MH - Female MH - Humans MH - Ileum/metabolism MH - Inflammatory Bowel Diseases/*metabolism/*pathology MH - Intestinal Mucosa/*metabolism/pathology MH - Male MH - Mast Cells/*metabolism/*pathology MH - Mice, Inbred BALB C MH - Middle Aged MH - Receptors, Vasoactive Intestinal Polypeptide, Type I/*biosynthesis/genetics MH - Up-Regulation MH - Vasoactive Intestinal Peptide/*biosynthesis MH - Young Adult OTO - NOTNLM OT - Crohn's disease OT - inflammation OT - neuro-immune interactions OT - ulcerative colitis EDAT- 2018/11/09 06:00 MHDA- 2020/01/23 06:00 CRDT- 2018/11/09 06:00 PHST- 2018/05/03 00:00 [received] PHST- 2018/09/24 00:00 [revised] PHST- 2018/10/07 00:00 [accepted] PHST- 2018/11/09 06:00 [pubmed] PHST- 2020/01/23 06:00 [medline] PHST- 2018/11/09 06:00 [entrez] AID - 10.1111/nmo.13503 [doi] PST - ppublish SO - Neurogastroenterol Motil. 2019 Mar;31(3):e13503. doi: 10.1111/nmo.13503. Epub 2018 Nov 8.