Targeting IL-17A Improves the Dysmotility of the Small Intestine and Alleviates the Injury of the Interstitial Cells of Cajal during Sepsis
Intestinal dysmotility is a frequent complication during sepsis and plays an important role in the development of secondary infections and multiple organ failure. However, the central mechanisms underlying this process have not been well elucidated. Currently, effective therapies are still lacking f...
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doaj-bf2dcd4966d04a45a831edbb8e6fd16e2020-11-24T21:27:49ZengHindawi LimitedOxidative Medicine and Cellular Longevity1942-09001942-09942019-01-01201910.1155/2019/14757291475729Targeting IL-17A Improves the Dysmotility of the Small Intestine and Alleviates the Injury of the Interstitial Cells of Cajal during SepsisJing Li0Pengyu Kong1Chao Chen2Jing Tang3Xiaoming Jin4Jinglong Yan5Yufu Wang6Department of Pathology and Electron Microscopy Center, Faculty of Basic Medical Science, Harbin Medical University, Harbin, ChinaDepartment of Orthopedics, Second Affiliated Hospital, Harbin Medical University, Harbin, ChinaDepartment of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, CanadaDepartment of Pathology and Electron Microscopy Center, Faculty of Basic Medical Science, Harbin Medical University, Harbin, ChinaDepartment of Pathology and Electron Microscopy Center, Faculty of Basic Medical Science, Harbin Medical University, Harbin, ChinaDepartment of Orthopedics, Second Affiliated Hospital, Harbin Medical University, Harbin, ChinaDepartment of Orthopedics, Second Affiliated Hospital, Harbin Medical University, Harbin, ChinaIntestinal dysmotility is a frequent complication during sepsis and plays an important role in the development of secondary infections and multiple organ failure. However, the central mechanisms underlying this process have not been well elucidated. Currently, effective therapies are still lacking for the treatment of sepsis-induced intestinal dysmotility. In this study, we found that the activation of IL-17 signaling within the muscularis propria might be associated with dysmotility of the small intestine during polymicrobial sepsis. Furthermore, we demonstrated that targeting IL-17A partially rescued the motility of the small intestine and alleviated interstitial cells of Cajal (ICC) injury during sepsis. The blockade of IL-17A suppressed the dominant sepsis-induced infiltration of M1-polarized macrophages into the muscularis. Additionally, impaired ICC survival may be associated with the oxidative stress injury induced by dominant infiltration of M1-polarized macrophages. Our findings reveal the important role of the IL-17 signaling pathway in the small intestine during sepsis and provide clues for developing a novel therapeutic strategy for treating gastrointestinal dysmotility during sepsis.http://dx.doi.org/10.1155/2019/1475729 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jing Li Pengyu Kong Chao Chen Jing Tang Xiaoming Jin Jinglong Yan Yufu Wang |
spellingShingle |
Jing Li Pengyu Kong Chao Chen Jing Tang Xiaoming Jin Jinglong Yan Yufu Wang Targeting IL-17A Improves the Dysmotility of the Small Intestine and Alleviates the Injury of the Interstitial Cells of Cajal during Sepsis Oxidative Medicine and Cellular Longevity |
author_facet |
Jing Li Pengyu Kong Chao Chen Jing Tang Xiaoming Jin Jinglong Yan Yufu Wang |
author_sort |
Jing Li |
title |
Targeting IL-17A Improves the Dysmotility of the Small Intestine and Alleviates the Injury of the Interstitial Cells of Cajal during Sepsis |
title_short |
Targeting IL-17A Improves the Dysmotility of the Small Intestine and Alleviates the Injury of the Interstitial Cells of Cajal during Sepsis |
title_full |
Targeting IL-17A Improves the Dysmotility of the Small Intestine and Alleviates the Injury of the Interstitial Cells of Cajal during Sepsis |
title_fullStr |
Targeting IL-17A Improves the Dysmotility of the Small Intestine and Alleviates the Injury of the Interstitial Cells of Cajal during Sepsis |
title_full_unstemmed |
Targeting IL-17A Improves the Dysmotility of the Small Intestine and Alleviates the Injury of the Interstitial Cells of Cajal during Sepsis |
title_sort |
targeting il-17a improves the dysmotility of the small intestine and alleviates the injury of the interstitial cells of cajal during sepsis |
publisher |
Hindawi Limited |
series |
Oxidative Medicine and Cellular Longevity |
issn |
1942-0900 1942-0994 |
publishDate |
2019-01-01 |
description |
Intestinal dysmotility is a frequent complication during sepsis and plays an important role in the development of secondary infections and multiple organ failure. However, the central mechanisms underlying this process have not been well elucidated. Currently, effective therapies are still lacking for the treatment of sepsis-induced intestinal dysmotility. In this study, we found that the activation of IL-17 signaling within the muscularis propria might be associated with dysmotility of the small intestine during polymicrobial sepsis. Furthermore, we demonstrated that targeting IL-17A partially rescued the motility of the small intestine and alleviated interstitial cells of Cajal (ICC) injury during sepsis. The blockade of IL-17A suppressed the dominant sepsis-induced infiltration of M1-polarized macrophages into the muscularis. Additionally, impaired ICC survival may be associated with the oxidative stress injury induced by dominant infiltration of M1-polarized macrophages. Our findings reveal the important role of the IL-17 signaling pathway in the small intestine during sepsis and provide clues for developing a novel therapeutic strategy for treating gastrointestinal dysmotility during sepsis. |
url |
http://dx.doi.org/10.1155/2019/1475729 |
work_keys_str_mv |
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