Intestinal Epithelium-Derived Luminally Released Extracellular Vesicles in Sepsis Exhibit the Ability to Suppress TNF-α and IL-17A Expression in Mucosal Inflammation
Sepsis is a systemic inflammatory disorder induced by a dysregulated immune response to infection resulting in dysfunction of multiple critical organs, including the intestines. Previous studies have reported contrasting results regarding the abilities of exosomes circulating in the blood of sepsis...
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| Format: | Article |
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MDPI AG
2020-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/22/8445 |
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| author | Michael G. Appiah Eun Jeong Park Samuel Darkwah Eiji Kawamoto Yuichi Akama Arong Gaowa Manisha Kalsan Shandar Ahmad Motomu Shimaoka |
| author_facet | Michael G. Appiah Eun Jeong Park Samuel Darkwah Eiji Kawamoto Yuichi Akama Arong Gaowa Manisha Kalsan Shandar Ahmad Motomu Shimaoka |
| author_sort | Michael G. Appiah |
| collection | DOAJ |
| description | Sepsis is a systemic inflammatory disorder induced by a dysregulated immune response to infection resulting in dysfunction of multiple critical organs, including the intestines. Previous studies have reported contrasting results regarding the abilities of exosomes circulating in the blood of sepsis mice and patients to either promote or suppress inflammation. Little is known about how the gut epithelial cell-derived exosomes released in the intestinal luminal space during sepsis affect mucosal inflammation. To study this question, we isolated extracellular vesicles (EVs) from intestinal lavage of septic mice. The EVs expressed typical exosomal (CD63 and CD9) and epithelial (EpCAM) markers, which were further increased by sepsis. Moreover, septic-EV injection into inflamed gut induced a significant reduction in the messaging of pro-inflammatory cytokines TNF-α and IL-17A. MicroRNA (miRNA) profiling and reverse transcription and quantitative polymerase chain reaction (RT-qPCR) revealed a sepsis-induced exosomal increase in multiple miRNAs, which putatively target <i>TNF-α</i> and <i>IL-17A</i>. These results imply that intestinal epithelial cell (IEC)-derived luminal EVs carry miRNAs that mitigate pro-inflammatory responses. Taken together, our study proposes a novel mechanism by which IEC EVs released during sepsis transfer regulatory miRNAs to cells, possibly contributing to the amelioration of gut inflammation. |
| first_indexed | 2024-03-10T14:57:50Z |
| format | Article |
| id | doaj.art-644c27359f5b40149522e013ee1fa1c3 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T14:57:50Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-644c27359f5b40149522e013ee1fa1c32023-11-20T20:28:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-11-012122844510.3390/ijms21228445Intestinal Epithelium-Derived Luminally Released Extracellular Vesicles in Sepsis Exhibit the Ability to Suppress TNF-α and IL-17A Expression in Mucosal InflammationMichael G. Appiah0Eun Jeong Park1Samuel Darkwah2Eiji Kawamoto3Yuichi Akama4Arong Gaowa5Manisha Kalsan6Shandar Ahmad7Motomu Shimaoka8Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, JapanDepartment of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, JapanDepartment of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, JapanDepartment of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, JapanDepartment of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, JapanDepartment of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, JapanSchool of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi 110067, IndiaSchool of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi 110067, IndiaDepartment of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, JapanSepsis is a systemic inflammatory disorder induced by a dysregulated immune response to infection resulting in dysfunction of multiple critical organs, including the intestines. Previous studies have reported contrasting results regarding the abilities of exosomes circulating in the blood of sepsis mice and patients to either promote or suppress inflammation. Little is known about how the gut epithelial cell-derived exosomes released in the intestinal luminal space during sepsis affect mucosal inflammation. To study this question, we isolated extracellular vesicles (EVs) from intestinal lavage of septic mice. The EVs expressed typical exosomal (CD63 and CD9) and epithelial (EpCAM) markers, which were further increased by sepsis. Moreover, septic-EV injection into inflamed gut induced a significant reduction in the messaging of pro-inflammatory cytokines TNF-α and IL-17A. MicroRNA (miRNA) profiling and reverse transcription and quantitative polymerase chain reaction (RT-qPCR) revealed a sepsis-induced exosomal increase in multiple miRNAs, which putatively target <i>TNF-α</i> and <i>IL-17A</i>. These results imply that intestinal epithelial cell (IEC)-derived luminal EVs carry miRNAs that mitigate pro-inflammatory responses. Taken together, our study proposes a novel mechanism by which IEC EVs released during sepsis transfer regulatory miRNAs to cells, possibly contributing to the amelioration of gut inflammation.https://www.mdpi.com/1422-0067/21/22/8445sepsisintestinal epithelial cellsinflammationextracellular vesiclesTNF-αIL-17A |
| spellingShingle | Michael G. Appiah Eun Jeong Park Samuel Darkwah Eiji Kawamoto Yuichi Akama Arong Gaowa Manisha Kalsan Shandar Ahmad Motomu Shimaoka Intestinal Epithelium-Derived Luminally Released Extracellular Vesicles in Sepsis Exhibit the Ability to Suppress TNF-α and IL-17A Expression in Mucosal Inflammation International Journal of Molecular Sciences sepsis intestinal epithelial cells inflammation extracellular vesicles TNF-α IL-17A |
| title | Intestinal Epithelium-Derived Luminally Released Extracellular Vesicles in Sepsis Exhibit the Ability to Suppress TNF-α and IL-17A Expression in Mucosal Inflammation |
| title_full | Intestinal Epithelium-Derived Luminally Released Extracellular Vesicles in Sepsis Exhibit the Ability to Suppress TNF-α and IL-17A Expression in Mucosal Inflammation |
| title_fullStr | Intestinal Epithelium-Derived Luminally Released Extracellular Vesicles in Sepsis Exhibit the Ability to Suppress TNF-α and IL-17A Expression in Mucosal Inflammation |
| title_full_unstemmed | Intestinal Epithelium-Derived Luminally Released Extracellular Vesicles in Sepsis Exhibit the Ability to Suppress TNF-α and IL-17A Expression in Mucosal Inflammation |
| title_short | Intestinal Epithelium-Derived Luminally Released Extracellular Vesicles in Sepsis Exhibit the Ability to Suppress TNF-α and IL-17A Expression in Mucosal Inflammation |
| title_sort | intestinal epithelium derived luminally released extracellular vesicles in sepsis exhibit the ability to suppress tnf α and il 17a expression in mucosal inflammation |
| topic | sepsis intestinal epithelial cells inflammation extracellular vesicles TNF-α IL-17A |
| url | https://www.mdpi.com/1422-0067/21/22/8445 |
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