Anti-inflammatory Effects of Fungal Metabolites in Mouse Intestine as Revealed by In vitro Models
Inflammatory bowel diseases (IBD), which include Crohn's disease and ulcerative colitis, are chronic inflammatory disorders that can affect the whole gastrointestinal tract or the colonic mucosal layer. Current therapies aiming to suppress the exaggerated immune response in IBD largely rely on...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-08-01
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| Series: | Frontiers in Physiology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fphys.2017.00566/full |
| _version_ | 1818948811474599936 |
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| author | Dominik Schreiber Dominik Schreiber Lisa Marx Silke Felix Jasmin Clasohm Maximilian Weyland Maximilian Schäfer Markus Klotz Rainer Lilischkis Gerhard Erkel Karl-Herbert Schäfer Karl-Herbert Schäfer |
| author_facet | Dominik Schreiber Dominik Schreiber Lisa Marx Silke Felix Jasmin Clasohm Maximilian Weyland Maximilian Schäfer Markus Klotz Rainer Lilischkis Gerhard Erkel Karl-Herbert Schäfer Karl-Herbert Schäfer |
| author_sort | Dominik Schreiber |
| collection | DOAJ |
| description | Inflammatory bowel diseases (IBD), which include Crohn's disease and ulcerative colitis, are chronic inflammatory disorders that can affect the whole gastrointestinal tract or the colonic mucosal layer. Current therapies aiming to suppress the exaggerated immune response in IBD largely rely on compounds with non-satisfying effects or side-effects. Therefore, new therapeutical options are needed. In the present study, we investigated the anti-inflammatory effects of the fungal metabolites, galiellalactone, and dehydrocurvularin in both an in vitro intestinal inflammation model, as well as in isolated myenteric plexus and enterocyte cells. Administration of a pro-inflammatory cytokine mix through the mesenteric artery of intestinal segments caused an up-regulation of inflammatory marker genes. Treatment of the murine intestinal segments with galiellalactone or dehydrocurvularin by application through the mesenteric artery significantly prevented the expression of pro-inflammatory marker genes on the mRNA and the protein level. Comparable to the results in the perfused intestine model, treatment of primary enteric nervous system (ENS) cells from the murine intestine with the fungal compounds reduced expression of cytokines such as IL-6, TNF-α, IL-1β, and inflammatory enzymes such as COX-2 and iNOS on mRNA and protein levels. Similar anti-inflammatory effects of the fungal metabolites were observed in the human colorectal adenocarcinoma cell line DLD-1 after stimulation with IFN-γ (10 ng/ml), TNF-α (10 ng/ml), and IL-1β (5 ng/ml). Our results show that the mesenterially perfused intestine model provides a reliable tool for the screening of new therapeutics with limited amounts of test compounds. Furthermore, we could characterize the anti-inflammatory effects of two novel active compounds, galiellalactone, and dehydrocurvularin which are interesting candidates for studies with chronic animal models of IBD. |
| first_indexed | 2024-12-20T08:52:44Z |
| format | Article |
| id | doaj.art-05ae6787b8734e10b322bdfecbccdc7a |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-20T08:52:44Z |
| publishDate | 2017-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-05ae6787b8734e10b322bdfecbccdc7a2022-12-21T19:46:05ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2017-08-01810.3389/fphys.2017.00566283634Anti-inflammatory Effects of Fungal Metabolites in Mouse Intestine as Revealed by In vitro ModelsDominik Schreiber0Dominik Schreiber1Lisa Marx2Silke Felix3Jasmin Clasohm4Maximilian Weyland5Maximilian Schäfer6Markus Klotz7Rainer Lilischkis8Gerhard Erkel9Karl-Herbert Schäfer10Karl-Herbert Schäfer11Department of Biotechnology, University of Applied Sciences KaiserslauternKaiserslautern, GermanyDepartment of Biotechnology, Technical University of KaiserslauternKaiserslautern, GermanyDepartment of Biotechnology, University of Applied Sciences KaiserslauternKaiserslautern, GermanyDepartment of Biotechnology, Technical University of KaiserslauternKaiserslautern, GermanyDepartment of Biotechnology, University of Applied Sciences KaiserslauternKaiserslautern, GermanyDepartment of Biotechnology, University of Applied Sciences KaiserslauternKaiserslautern, GermanyDepartment of Biotechnology, University of Applied Sciences KaiserslauternKaiserslautern, GermanyDepartment of Biotechnology, University of Applied Sciences KaiserslauternKaiserslautern, GermanyDepartment of Biotechnology, University of Applied Sciences KaiserslauternKaiserslautern, GermanyDepartment of Biotechnology, Technical University of KaiserslauternKaiserslautern, GermanyDepartment of Biotechnology, University of Applied Sciences KaiserslauternKaiserslautern, GermanyPediatric Surgery, University Hospital MannheimMannheim, GermanyInflammatory bowel diseases (IBD), which include Crohn's disease and ulcerative colitis, are chronic inflammatory disorders that can affect the whole gastrointestinal tract or the colonic mucosal layer. Current therapies aiming to suppress the exaggerated immune response in IBD largely rely on compounds with non-satisfying effects or side-effects. Therefore, new therapeutical options are needed. In the present study, we investigated the anti-inflammatory effects of the fungal metabolites, galiellalactone, and dehydrocurvularin in both an in vitro intestinal inflammation model, as well as in isolated myenteric plexus and enterocyte cells. Administration of a pro-inflammatory cytokine mix through the mesenteric artery of intestinal segments caused an up-regulation of inflammatory marker genes. Treatment of the murine intestinal segments with galiellalactone or dehydrocurvularin by application through the mesenteric artery significantly prevented the expression of pro-inflammatory marker genes on the mRNA and the protein level. Comparable to the results in the perfused intestine model, treatment of primary enteric nervous system (ENS) cells from the murine intestine with the fungal compounds reduced expression of cytokines such as IL-6, TNF-α, IL-1β, and inflammatory enzymes such as COX-2 and iNOS on mRNA and protein levels. Similar anti-inflammatory effects of the fungal metabolites were observed in the human colorectal adenocarcinoma cell line DLD-1 after stimulation with IFN-γ (10 ng/ml), TNF-α (10 ng/ml), and IL-1β (5 ng/ml). Our results show that the mesenterially perfused intestine model provides a reliable tool for the screening of new therapeutics with limited amounts of test compounds. Furthermore, we could characterize the anti-inflammatory effects of two novel active compounds, galiellalactone, and dehydrocurvularin which are interesting candidates for studies with chronic animal models of IBD.http://journal.frontiersin.org/article/10.3389/fphys.2017.00566/fullinflammatory bowel diseasemesenterial perfusiongaliellalactonedehydrocurvularindexamethasoneENS |
| spellingShingle | Dominik Schreiber Dominik Schreiber Lisa Marx Silke Felix Jasmin Clasohm Maximilian Weyland Maximilian Schäfer Markus Klotz Rainer Lilischkis Gerhard Erkel Karl-Herbert Schäfer Karl-Herbert Schäfer Anti-inflammatory Effects of Fungal Metabolites in Mouse Intestine as Revealed by In vitro Models Frontiers in Physiology inflammatory bowel disease mesenterial perfusion galiellalactone dehydrocurvularin dexamethasone ENS |
| title | Anti-inflammatory Effects of Fungal Metabolites in Mouse Intestine as Revealed by In vitro Models |
| title_full | Anti-inflammatory Effects of Fungal Metabolites in Mouse Intestine as Revealed by In vitro Models |
| title_fullStr | Anti-inflammatory Effects of Fungal Metabolites in Mouse Intestine as Revealed by In vitro Models |
| title_full_unstemmed | Anti-inflammatory Effects of Fungal Metabolites in Mouse Intestine as Revealed by In vitro Models |
| title_short | Anti-inflammatory Effects of Fungal Metabolites in Mouse Intestine as Revealed by In vitro Models |
| title_sort | anti inflammatory effects of fungal metabolites in mouse intestine as revealed by in vitro models |
| topic | inflammatory bowel disease mesenterial perfusion galiellalactone dehydrocurvularin dexamethasone ENS |
| url | http://journal.frontiersin.org/article/10.3389/fphys.2017.00566/full |
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