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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Bibliographic Details
Published in:Oxidative medicine and cellular longevity 2019, Vol.2019 (2019), p.1-15
Main Authors: Wang, Yufu, Jin, Xiaoming, Tang, Jing, Chen, Chao, Kong, Pengyu, Li, Jing, Yan, Jinglong
Format: Article
Language:English
Subjects:
Amobarbital
Animals
Colon
Cytokines
Female
Gastrointestinal Motility - immunology
Health aspects
Immunology
Infection
Inflammation
Interleukin-17 - antagonists & inhibitors
Interleukin-17 - immunology
Interstitial Cells of Cajal - immunology
Interstitial Cells of Cajal - pathology
Intestine, Small - immunology
Intestine, Small - injuries
Intestine, Small - pathology
Kinases
Laboratory animals
Male
Mice
Microscopy
Motility
Neutrophils
Nitric oxide
Pathogenesis
RAW 264.7 Cells
Rodents
Sepsis
Sepsis - immunology
Sepsis - pathology
Signal Transduction - immunology
Small intestine
Tumor necrosis factor-TNF
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Summary: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.
ISSN:1942-0900
1942-0994
DOI:10.1155/2019/1475729