Depletion of muscularis macrophages ameliorates inflammation-driven dysmotility in murine colitis model
Abstract Previously, the presence of a blood-myenteric plexus barrier and its disruption was reported in experimentally induced colitis via a macrophage-dependent process. The aim of this study is to reveal how myenteric barrier disruption and subsequent neuronal injury affects gut motility in vivo...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-50059-7 |
| _version_ | 1797377056117358592 |
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| author | Szilamér Ferenczi Fruzsina Mogor Peter Takacs Tamas Kovacs Viktoria E. Toth Zoltán V. Varga Krisztina Kovács Zoltan Lohinai Koppány Csaba Vass Nandor Nagy David Dora |
| author_facet | Szilamér Ferenczi Fruzsina Mogor Peter Takacs Tamas Kovacs Viktoria E. Toth Zoltán V. Varga Krisztina Kovács Zoltan Lohinai Koppány Csaba Vass Nandor Nagy David Dora |
| author_sort | Szilamér Ferenczi |
| collection | DOAJ |
| description | Abstract Previously, the presence of a blood-myenteric plexus barrier and its disruption was reported in experimentally induced colitis via a macrophage-dependent process. The aim of this study is to reveal how myenteric barrier disruption and subsequent neuronal injury affects gut motility in vivo in a murine colitis model. We induced colitis with dextran sulfate sodium (DSS), with the co-administration of liposome-encapsulated clodronate (l-clodronate) to simultaneously deplete blood monocytes contributing to macrophage infiltration in the inflamed muscularis of experimental mice. DSS-treated animals receiving concurrent l-clodronate injection showed significantly decreased blood monocyte numbers and colon muscularis macrophage (MM) density compared to DSS-treated control (DSS-vehicle). DSS-clodronate-treated mice exhibited significantly slower whole gut transit time than DSS-vehicle-treated animals and comparable to that of controls. Experiments with oral gavage-fed Evans-blue dye showed similar whole gut transit times in DSS-clodronate-treated mice as in control animals. Furthermore, qPCR-analysis and immunofluorescence on colon muscularis samples revealed that factors associated with neuroinflammation and neurodegeneration, including Bax1, Hdac4, IL-18, Casp8 and Hif1a are overexpressed after DSS-treatment, but not in the case of concurrent l-clodronate administration. Our findings highlight that MM-infiltration in the muscularis layer is responsible for colitis-associated dysmotility and enteric neuronal dysfunction along with the release of mediators associated with neurodegeneration in a murine experimental model. |
| first_indexed | 2024-03-08T19:48:28Z |
| format | Article |
| id | doaj.art-886c13f3f37d4de5af40aeac9394aa98 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-08T19:48:28Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-886c13f3f37d4de5af40aeac9394aa982023-12-24T12:14:50ZengNature PortfolioScientific Reports2045-23222023-12-0113111510.1038/s41598-023-50059-7Depletion of muscularis macrophages ameliorates inflammation-driven dysmotility in murine colitis modelSzilamér Ferenczi0Fruzsina Mogor1Peter Takacs2Tamas Kovacs3Viktoria E. Toth4Zoltán V. Varga5Krisztina Kovács6Zoltan Lohinai7Koppány Csaba Vass8Nandor Nagy9David Dora10Institute of Experimental Medicine, Laboratory of Molecular NeuroendocrinologyDepartment of Anatomy, Histology and Embryology, Semmelweis UniversityDepartment of Anatomy, Histology and Embryology, Semmelweis UniversityDepartment of Anatomy, Histology and Embryology, Semmelweis UniversityDepartment of Pharmacology and Pharmacotherapy, Semmelweis UniversityDepartment of Pharmacology and Pharmacotherapy, Semmelweis UniversityInstitute of Experimental Medicine, Laboratory of Molecular NeuroendocrinologyTranslational Medicine Institute, Semmelweis UniversityDepartment of Laboratory Medicine, Semmelweis UniversityDepartment of Anatomy, Histology and Embryology, Semmelweis UniversityDepartment of Anatomy, Histology and Embryology, Semmelweis UniversityAbstract Previously, the presence of a blood-myenteric plexus barrier and its disruption was reported in experimentally induced colitis via a macrophage-dependent process. The aim of this study is to reveal how myenteric barrier disruption and subsequent neuronal injury affects gut motility in vivo in a murine colitis model. We induced colitis with dextran sulfate sodium (DSS), with the co-administration of liposome-encapsulated clodronate (l-clodronate) to simultaneously deplete blood monocytes contributing to macrophage infiltration in the inflamed muscularis of experimental mice. DSS-treated animals receiving concurrent l-clodronate injection showed significantly decreased blood monocyte numbers and colon muscularis macrophage (MM) density compared to DSS-treated control (DSS-vehicle). DSS-clodronate-treated mice exhibited significantly slower whole gut transit time than DSS-vehicle-treated animals and comparable to that of controls. Experiments with oral gavage-fed Evans-blue dye showed similar whole gut transit times in DSS-clodronate-treated mice as in control animals. Furthermore, qPCR-analysis and immunofluorescence on colon muscularis samples revealed that factors associated with neuroinflammation and neurodegeneration, including Bax1, Hdac4, IL-18, Casp8 and Hif1a are overexpressed after DSS-treatment, but not in the case of concurrent l-clodronate administration. Our findings highlight that MM-infiltration in the muscularis layer is responsible for colitis-associated dysmotility and enteric neuronal dysfunction along with the release of mediators associated with neurodegeneration in a murine experimental model.https://doi.org/10.1038/s41598-023-50059-7 |
| spellingShingle | Szilamér Ferenczi Fruzsina Mogor Peter Takacs Tamas Kovacs Viktoria E. Toth Zoltán V. Varga Krisztina Kovács Zoltan Lohinai Koppány Csaba Vass Nandor Nagy David Dora Depletion of muscularis macrophages ameliorates inflammation-driven dysmotility in murine colitis model Scientific Reports |
| title | Depletion of muscularis macrophages ameliorates inflammation-driven dysmotility in murine colitis model |
| title_full | Depletion of muscularis macrophages ameliorates inflammation-driven dysmotility in murine colitis model |
| title_fullStr | Depletion of muscularis macrophages ameliorates inflammation-driven dysmotility in murine colitis model |
| title_full_unstemmed | Depletion of muscularis macrophages ameliorates inflammation-driven dysmotility in murine colitis model |
| title_short | Depletion of muscularis macrophages ameliorates inflammation-driven dysmotility in murine colitis model |
| title_sort | depletion of muscularis macrophages ameliorates inflammation driven dysmotility in murine colitis model |
| url | https://doi.org/10.1038/s41598-023-50059-7 |
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