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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Main Authors: Jing Li, Pengyu Kong, Chao Chen, Jing Tang, Xiaoming Jin, Jinglong Yan, Yufu Wang
Format: Article
Language:English
Published: Hindawi Limited 2019-01-01
Series:Oxidative Medicine and Cellular Longevity
Online Access:http://dx.doi.org/10.1155/2019/1475729
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spelling 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
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