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IL-37b alleviates endothelial cell apoptosis and inflammation in Kawasaki disease through IL-1R8 pathway

Kawasaki disease (KD) is an acute vasculitis of pediatric populations that may develop coronary artery aneurysms if untreated. It has been regarded as the principal cause of acquired heart disease in children of the developed countries. Interleukin (IL)-37, as one of the IL-1 family members, is a na...

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Autores principales: Jia, Chang, Zhuge, Yingzhi, Zhang, Shuchi, Ni, Chao, Wang, Linlin, Wu, Rongzhou, Niu, Chao, Wen, Zhengwang, Rong, Xing, Qiu, Huixian, Chu, Maoping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174541/
https://www.ncbi.nlm.nih.gov/pubmed/34083516
http://dx.doi.org/10.1038/s41419-021-03852-z
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author Jia, Chang
Zhuge, Yingzhi
Zhang, Shuchi
Ni, Chao
Wang, Linlin
Wu, Rongzhou
Niu, Chao
Wen, Zhengwang
Rong, Xing
Qiu, Huixian
Chu, Maoping
author_facet Jia, Chang
Zhuge, Yingzhi
Zhang, Shuchi
Ni, Chao
Wang, Linlin
Wu, Rongzhou
Niu, Chao
Wen, Zhengwang
Rong, Xing
Qiu, Huixian
Chu, Maoping
author_sort Jia, Chang
collection PubMed
description Kawasaki disease (KD) is an acute vasculitis of pediatric populations that may develop coronary artery aneurysms if untreated. It has been regarded as the principal cause of acquired heart disease in children of the developed countries. Interleukin (IL)-37, as one of the IL-1 family members, is a natural suppressor of inflammation that is caused by activation of innate and adaptive immunity. However, detailed roles of IL-37 in KD are largely unclear. Sera from patients with KD displayed that IL-37 level was significantly decreased compared with healthy controls (HCs). QRT-PCR and western blot analyses showed that the expression level of IL-37 variant, IL-37b, was remarkably downregulated in human umbilical vein endothelial cells (HUVECs) exposed to KD sera-treated THP1 cells. Therefore, we researched the role of IL-37b in the context of KD and hypothesized that IL-37b may have a powerful protective effect in KD patients. We first observed and substantiated the protective role of IL-37b in a mouse model of KD induced by Candida albicans cell wall extracts (CAWS). In vitro experiments demonstrated that IL-37b alleviated endothelial cell apoptosis and inflammation via IL-1R8 receptor by inhibiting ERK and NFκB activation, which were also recapitulated in the KD mouse model. Together, our findings suggest that IL-37b play an effective protective role in coronary endothelial damage in KD, providing new evidence that IL-37b is a potential candidate drug to treat KD.
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spelling pubmed-81745412021-06-04 IL-37b alleviates endothelial cell apoptosis and inflammation in Kawasaki disease through IL-1R8 pathway Jia, Chang Zhuge, Yingzhi Zhang, Shuchi Ni, Chao Wang, Linlin Wu, Rongzhou Niu, Chao Wen, Zhengwang Rong, Xing Qiu, Huixian Chu, Maoping Cell Death Dis Article Kawasaki disease (KD) is an acute vasculitis of pediatric populations that may develop coronary artery aneurysms if untreated. It has been regarded as the principal cause of acquired heart disease in children of the developed countries. Interleukin (IL)-37, as one of the IL-1 family members, is a natural suppressor of inflammation that is caused by activation of innate and adaptive immunity. However, detailed roles of IL-37 in KD are largely unclear. Sera from patients with KD displayed that IL-37 level was significantly decreased compared with healthy controls (HCs). QRT-PCR and western blot analyses showed that the expression level of IL-37 variant, IL-37b, was remarkably downregulated in human umbilical vein endothelial cells (HUVECs) exposed to KD sera-treated THP1 cells. Therefore, we researched the role of IL-37b in the context of KD and hypothesized that IL-37b may have a powerful protective effect in KD patients. We first observed and substantiated the protective role of IL-37b in a mouse model of KD induced by Candida albicans cell wall extracts (CAWS). In vitro experiments demonstrated that IL-37b alleviated endothelial cell apoptosis and inflammation via IL-1R8 receptor by inhibiting ERK and NFκB activation, which were also recapitulated in the KD mouse model. Together, our findings suggest that IL-37b play an effective protective role in coronary endothelial damage in KD, providing new evidence that IL-37b is a potential candidate drug to treat KD. Nature Publishing Group UK 2021-06-03 /pmc/articles/PMC8174541/ /pubmed/34083516 http://dx.doi.org/10.1038/s41419-021-03852-z Text en © The Author(s) 2021, corrected publication 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Jia, Chang
Zhuge, Yingzhi
Zhang, Shuchi
Ni, Chao
Wang, Linlin
Wu, Rongzhou
Niu, Chao
Wen, Zhengwang
Rong, Xing
Qiu, Huixian
Chu, Maoping
IL-37b alleviates endothelial cell apoptosis and inflammation in Kawasaki disease through IL-1R8 pathway
title IL-37b alleviates endothelial cell apoptosis and inflammation in Kawasaki disease through IL-1R8 pathway
title_full IL-37b alleviates endothelial cell apoptosis and inflammation in Kawasaki disease through IL-1R8 pathway
title_fullStr IL-37b alleviates endothelial cell apoptosis and inflammation in Kawasaki disease through IL-1R8 pathway
title_full_unstemmed IL-37b alleviates endothelial cell apoptosis and inflammation in Kawasaki disease through IL-1R8 pathway
title_short IL-37b alleviates endothelial cell apoptosis and inflammation in Kawasaki disease through IL-1R8 pathway
title_sort il-37b alleviates endothelial cell apoptosis and inflammation in kawasaki disease through il-1r8 pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174541/
https://www.ncbi.nlm.nih.gov/pubmed/34083516
http://dx.doi.org/10.1038/s41419-021-03852-z
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