GLP-1 Induces Barrier Protective Expression in Brunner's Glands and Regulates Colonic Inflammation. Issue 9 (September 2016)

• Record Type: Journal Article
• Authors: Bang-Berthelsen, Claus H.; Holm, Thomas L.; Pyke, Charles; Simonsen, Lotte; Søkilde, Rolf; Pociot, Flemming; Heller, R. Scott; Folkersen, Lasse; Kvist, Peter H.; Jackerott, Malene; Fleckner, Jan; Vilién, Mogens; Knudsen, Lotte B.; Heding, Anders; Frederiksen, Klaus S.
• Is Part Of: Inflammatory bowel diseases. Volume 22:Issue 9(2016:Sep.)
• Publication Date: 2016-09
• Subjects: IL-33 -- Brunner's glands -- inflammatory bowel disease -- GLP-1 -- MUC5B; Inflammatory bowel diseases -- Periodicals; Colitis, Ulcerative -- Periodicals; Crohn Disease -- Periodicals; Inflammatory Bowel Diseases -- Periodicals; 616.344
• DOI: 10.1097/MIB.0000000000000847
• Languages: English
• ISSNs: 1078-0998

Abstract

Abstract : Background: Beneficial roles for glucagon-like peptide 1 (GLP-1)/GLP-1R signaling have recently been described in diseases, where low-grade inflammation is a common phenomenon. We investigated the effects of GLP-1 in Brunner's glands and duodenum with abundant expression of GLP-1 receptors, as well as GLP-1 effect on colonic inflammation. Methods: RNA from Brunner's glands of GLP-1R knockout and wild-type mice were subjected to full transcriptome profiling. Array results were validated by quantitative reverse transcription polymerase chain reaction in wild-type mice and compared with samples from inflammatory bowel disease (IBD) patients and controls. In addition, we performed a detailed investigation of the effects of exogenous liraglutide dosing in a T-cell driven adoptive transfer (AdTr) colitis mouse model. Results: Analyses of the Brunner's gland transcriptomes of GLP-1R knockout and wild-type mice identified 722 differentially expressed genes. Upregulated transcripts after GLP-1 dosing included IL-33, chemokine ligand 20 (CCL20), and mucin 5b. Biopsies from IBD patients and controls, as well as data from the AdTr model, showed deregulated expression of GLP-1R, CCL20, and IL-33 in colon. Circulating levels of GLP-1 were found to be increased in mice with colitis. Finally, the colonic cytokine levels and disease scores of the AdTr model indicated reduced levels of colonic inflammation in liraglutide-dosed animals. Conclusions: We demonstrate that IL-33, GLP-1R, and CCL20 are deregulated in human IBD, and that prophylactic treatment with 0.6 mg/kg liraglutide improves disease in AdTr colitis. In addition, GLP-1 receptor agonists upregulate IL-33, mucin 5b, and CCL20 in murine Brunner's glands. Taken together, our data indicate that GLP-1 receptor agonists affect gut homeostasis in both proximal and distal parts of the gut. Abstract : Supplemental Digital Content Is Available in the Text.Article first published online 10 August 2016.