Galanin receptor 3 attenuates inflammation and influences the gut microbiota in an experimental murine colitis model
Abstract The regulatory (neuro)peptide galanin and its three receptors (GAL1–3R) are involved in immunity and inflammation. Galanin alleviated inflammatory bowel disease (IBD) in rats. However, studies on the galanin receptors involved are lacking. We aimed to determine galanin receptor expression i...
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Nature Portfolio
2021
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oai:doaj.org-article:161035a679d44772a3030f3cd7ee332e2021-12-02T14:12:41ZGalanin receptor 3 attenuates inflammation and influences the gut microbiota in an experimental murine colitis model10.1038/s41598-020-79456-y2045-2322https://doaj.org/article/161035a679d44772a3030f3cd7ee332e2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79456-yhttps://doaj.org/toc/2045-2322Abstract The regulatory (neuro)peptide galanin and its three receptors (GAL1–3R) are involved in immunity and inflammation. Galanin alleviated inflammatory bowel disease (IBD) in rats. However, studies on the galanin receptors involved are lacking. We aimed to determine galanin receptor expression in IBD patients and to evaluate if GAL2R and GAL3R contribute to murine colitis. Immunohistochemical analysis revealed that granulocytes in colon specimens of IBD patients (Crohn’s disease and ulcerative colitis) expressed GAL2R and GAL3R but not GAL1R. After colitis induction with 2% dextran sulfate sodium (DSS) for 7 days, mice lacking GAL3R (GAL3R-KO) lost more body weight, exhibited more severe colonic inflammation and aggravated histologic damage, with increased infiltration of neutrophils compared to wild-type animals. Loss of GAL3R resulted in higher local and systemic inflammatory cytokine/chemokine levels. Remarkably, colitis-associated changes to the intestinal microbiota, as assessed by quantitative culture-independent techniques, were most pronounced in GAL3R-KO mice, characterized by elevated numbers of enterobacteria and bifidobacteria. In contrast, GAL2R deletion did not influence the course of colitis. In conclusion, granulocyte GAL2R and GAL3R expression is related to IBD activity in humans, and DSS-induced colitis in mice is strongly affected by GAL3R loss. Consequently, GAL3R poses a novel therapeutic target for IBD.Susanne M. BrunnerFlorian ReichmannJulia LeitnerSoraya WölflStefan BereswillAitak FarziAnna-Maria SchneiderEckhard KlieserDaniel NeureiterMichael EmbergerMarkus M. HeimesaatDaniel WeghuberRoland LangPeter HolzerBarbara KoflerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021) |
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Medicine R Science Q Susanne M. Brunner Florian Reichmann Julia Leitner Soraya Wölfl Stefan Bereswill Aitak Farzi Anna-Maria Schneider Eckhard Klieser Daniel Neureiter Michael Emberger Markus M. Heimesaat Daniel Weghuber Roland Lang Peter Holzer Barbara Kofler Galanin receptor 3 attenuates inflammation and influences the gut microbiota in an experimental murine colitis model |
| description |
Abstract The regulatory (neuro)peptide galanin and its three receptors (GAL1–3R) are involved in immunity and inflammation. Galanin alleviated inflammatory bowel disease (IBD) in rats. However, studies on the galanin receptors involved are lacking. We aimed to determine galanin receptor expression in IBD patients and to evaluate if GAL2R and GAL3R contribute to murine colitis. Immunohistochemical analysis revealed that granulocytes in colon specimens of IBD patients (Crohn’s disease and ulcerative colitis) expressed GAL2R and GAL3R but not GAL1R. After colitis induction with 2% dextran sulfate sodium (DSS) for 7 days, mice lacking GAL3R (GAL3R-KO) lost more body weight, exhibited more severe colonic inflammation and aggravated histologic damage, with increased infiltration of neutrophils compared to wild-type animals. Loss of GAL3R resulted in higher local and systemic inflammatory cytokine/chemokine levels. Remarkably, colitis-associated changes to the intestinal microbiota, as assessed by quantitative culture-independent techniques, were most pronounced in GAL3R-KO mice, characterized by elevated numbers of enterobacteria and bifidobacteria. In contrast, GAL2R deletion did not influence the course of colitis. In conclusion, granulocyte GAL2R and GAL3R expression is related to IBD activity in humans, and DSS-induced colitis in mice is strongly affected by GAL3R loss. Consequently, GAL3R poses a novel therapeutic target for IBD. |
| format |
article |
| author |
Susanne M. Brunner Florian Reichmann Julia Leitner Soraya Wölfl Stefan Bereswill Aitak Farzi Anna-Maria Schneider Eckhard Klieser Daniel Neureiter Michael Emberger Markus M. Heimesaat Daniel Weghuber Roland Lang Peter Holzer Barbara Kofler |
| author_facet |
Susanne M. Brunner Florian Reichmann Julia Leitner Soraya Wölfl Stefan Bereswill Aitak Farzi Anna-Maria Schneider Eckhard Klieser Daniel Neureiter Michael Emberger Markus M. Heimesaat Daniel Weghuber Roland Lang Peter Holzer Barbara Kofler |
| author_sort |
Susanne M. Brunner |
| title |
Galanin receptor 3 attenuates inflammation and influences the gut microbiota in an experimental murine colitis model |
| title_short |
Galanin receptor 3 attenuates inflammation and influences the gut microbiota in an experimental murine colitis model |
| title_full |
Galanin receptor 3 attenuates inflammation and influences the gut microbiota in an experimental murine colitis model |
| title_fullStr |
Galanin receptor 3 attenuates inflammation and influences the gut microbiota in an experimental murine colitis model |
| title_full_unstemmed |
Galanin receptor 3 attenuates inflammation and influences the gut microbiota in an experimental murine colitis model |
| title_sort |
galanin receptor 3 attenuates inflammation and influences the gut microbiota in an experimental murine colitis model |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/161035a679d44772a3030f3cd7ee332e |
| work_keys_str_mv |
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