Abstract
| Original language | English |
|---|---|
| Journal | Inflammatory Bowel Diseases |
| Volume | 22 |
| Issue number | 9 |
| Pages (from-to) | 2078-2097 |
| Number of pages | 20 |
| ISSN | 1078-0998 |
| DOIs | |
| Publication status | Published - 2016 |
Keywords
- IL-33
- Brunner's glands
- Inflammatory bowel disease
- GLP-1
- MUC5B
Cite this
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GLP-1 Induces Barrier Protective Expression in Brunner's Glands and Regulates Colonic Inflammation. / Bang-Berthelsen, Claus Heiner; Holm, Thomas L.; Pyke, Charles; Simonsen, Lotte; Sokilde, Rolf; Pociot, Flemming; Heller, R. Scott; Folkersen, Lasse; Kvist, Peter H.; Jackerott, Malene; Fleckner, Jan; Vilien, Mogens; Knudsen, Lotte B.; Heding, Anders; Frederiksen, Klaus S.
In: Inflammatory Bowel Diseases, Vol. 22, No. 9, 2016, p. 2078-2097.Research output: Contribution to journal › Journal article › Research › peer-review
TY - JOUR
T1 - GLP-1 Induces Barrier Protective Expression in Brunner's Glands and Regulates Colonic Inflammation
AU - Bang-Berthelsen, Claus Heiner
AU - Holm, Thomas L.
AU - Pyke, Charles
AU - Simonsen, Lotte
AU - Sokilde, Rolf
AU - Pociot, Flemming
AU - Heller, R. Scott
AU - Folkersen, Lasse
AU - Kvist, Peter H.
AU - Jackerott, Malene
AU - Fleckner, Jan
AU - Vilien, Mogens
AU - Knudsen, Lotte B.
AU - Heding, Anders
AU - Frederiksen, Klaus S.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - IL-33
KW - Brunner's glands
KW - Inflammatory bowel disease
KW - GLP-1
KW - MUC5B
U2 - 10.1097/MIB.0000000000000847
DO - 10.1097/MIB.0000000000000847
M3 - Journal article
VL - 22
SP - 2078
EP - 2097
JO - Inflammatory Bowel Diseases
JF - Inflammatory Bowel Diseases
SN - 1078-0998
IS - 9
ER -