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Anti-Allergic Inflammatory Activity of Interleukin-37 Is Mediated by Novel Signaling Cascades in Human Eosinophils

IL-1 family regulatory cytokine IL-37b can suppress innate immunity and inflammatory activity in inflammatory diseases. In this study, IL-37b showed remarkable in vitro suppression of inflammatory tumor necrosis factor-α, IL-1β, IL-6, CCL2, and CXCL8 production in the coculture of human primary eosi...

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Autores principales: Zhu, Jing, Dong, Jie, Ji, Lu, Jiang, Peiyong, Leung, Ting Fan, Liu, Dehua, Ng, Lai Guan, Tsang, Miranda Sin-Man, Jiao, Delong, Lam, Christopher Wai-Kei, Wong, Chun-Kwok
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023969/
https://www.ncbi.nlm.nih.gov/pubmed/29988381
http://dx.doi.org/10.3389/fimmu.2018.01445
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author Zhu, Jing
Dong, Jie
Ji, Lu
Jiang, Peiyong
Leung, Ting Fan
Liu, Dehua
Ng, Lai Guan
Tsang, Miranda Sin-Man
Jiao, Delong
Lam, Christopher Wai-Kei
Wong, Chun-Kwok
author_facet Zhu, Jing
Dong, Jie
Ji, Lu
Jiang, Peiyong
Leung, Ting Fan
Liu, Dehua
Ng, Lai Guan
Tsang, Miranda Sin-Man
Jiao, Delong
Lam, Christopher Wai-Kei
Wong, Chun-Kwok
author_sort Zhu, Jing
collection PubMed
description IL-1 family regulatory cytokine IL-37b can suppress innate immunity and inflammatory activity in inflammatory diseases. In this study, IL-37b showed remarkable in vitro suppression of inflammatory tumor necrosis factor-α, IL-1β, IL-6, CCL2, and CXCL8 production in the coculture of human primary eosinophils and human bronchial epithelial BEAS-2B cells with the stimulation of bacterial toll-like receptor-2 ligand peptidoglycan, while antagonizing the activation of intracellular nuclear factor-κB, PI3K–Akt, extracellular signal-regulated kinase 1/2, and suppressing the gene transcription of allergic inflammation-related PYCARD, S100A9, and CAMP as demonstrated by flow cytometry, RNA-sequencing, and bioinformatics. Results therefore elucidated the novel anti-inflammation-related molecular mechanisms mediated by IL-37b. Using the house dust mite (HDM)-induced humanized asthmatic NOD/SCID mice for preclinical study, intravenous administration of IL-37b restored the normal plasma levels of eosinophil activators CCL11 and IL-5, suppressed the elevated concentrations of Th2 and asthma-related cytokines IL-4, IL-6, and IL-13 and inflammatory IL-17, CCL5, and CCL11 in lung homogenate of asthmatic mice. Histopathological results of lung tissue illustrated that IL-37b could mitigate the enhanced mucus, eosinophil infiltration, thickened airway wall, and goblet cells. Together with similar findings using the ovalbumin- and HDM-induced allergic asthmatic mice further validated the therapeutic potential of IL-37b in allergic asthma. The above results illustrate the novel IL-37-mediated regulation of intracellular inflammation mechanism linking bacterial infection and the activation of human eosinophils and confirm the in vivo anti-inflammatory activity of IL-37b on human allergic asthma.
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spelling pubmed-60239692018-07-09 Anti-Allergic Inflammatory Activity of Interleukin-37 Is Mediated by Novel Signaling Cascades in Human Eosinophils Zhu, Jing Dong, Jie Ji, Lu Jiang, Peiyong Leung, Ting Fan Liu, Dehua Ng, Lai Guan Tsang, Miranda Sin-Man Jiao, Delong Lam, Christopher Wai-Kei Wong, Chun-Kwok Front Immunol Immunology IL-1 family regulatory cytokine IL-37b can suppress innate immunity and inflammatory activity in inflammatory diseases. In this study, IL-37b showed remarkable in vitro suppression of inflammatory tumor necrosis factor-α, IL-1β, IL-6, CCL2, and CXCL8 production in the coculture of human primary eosinophils and human bronchial epithelial BEAS-2B cells with the stimulation of bacterial toll-like receptor-2 ligand peptidoglycan, while antagonizing the activation of intracellular nuclear factor-κB, PI3K–Akt, extracellular signal-regulated kinase 1/2, and suppressing the gene transcription of allergic inflammation-related PYCARD, S100A9, and CAMP as demonstrated by flow cytometry, RNA-sequencing, and bioinformatics. Results therefore elucidated the novel anti-inflammation-related molecular mechanisms mediated by IL-37b. Using the house dust mite (HDM)-induced humanized asthmatic NOD/SCID mice for preclinical study, intravenous administration of IL-37b restored the normal plasma levels of eosinophil activators CCL11 and IL-5, suppressed the elevated concentrations of Th2 and asthma-related cytokines IL-4, IL-6, and IL-13 and inflammatory IL-17, CCL5, and CCL11 in lung homogenate of asthmatic mice. Histopathological results of lung tissue illustrated that IL-37b could mitigate the enhanced mucus, eosinophil infiltration, thickened airway wall, and goblet cells. Together with similar findings using the ovalbumin- and HDM-induced allergic asthmatic mice further validated the therapeutic potential of IL-37b in allergic asthma. The above results illustrate the novel IL-37-mediated regulation of intracellular inflammation mechanism linking bacterial infection and the activation of human eosinophils and confirm the in vivo anti-inflammatory activity of IL-37b on human allergic asthma. Frontiers Media S.A. 2018-06-22 /pmc/articles/PMC6023969/ /pubmed/29988381 http://dx.doi.org/10.3389/fimmu.2018.01445 Text en Copyright © 2018 Zhu, Dong, Ji, Jiang, Leung, Liu, Ng, Tsang, Jiao, Lam and Wong. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Zhu, Jing
Dong, Jie
Ji, Lu
Jiang, Peiyong
Leung, Ting Fan
Liu, Dehua
Ng, Lai Guan
Tsang, Miranda Sin-Man
Jiao, Delong
Lam, Christopher Wai-Kei
Wong, Chun-Kwok
Anti-Allergic Inflammatory Activity of Interleukin-37 Is Mediated by Novel Signaling Cascades in Human Eosinophils
title Anti-Allergic Inflammatory Activity of Interleukin-37 Is Mediated by Novel Signaling Cascades in Human Eosinophils
title_full Anti-Allergic Inflammatory Activity of Interleukin-37 Is Mediated by Novel Signaling Cascades in Human Eosinophils
title_fullStr Anti-Allergic Inflammatory Activity of Interleukin-37 Is Mediated by Novel Signaling Cascades in Human Eosinophils
title_full_unstemmed Anti-Allergic Inflammatory Activity of Interleukin-37 Is Mediated by Novel Signaling Cascades in Human Eosinophils
title_short Anti-Allergic Inflammatory Activity of Interleukin-37 Is Mediated by Novel Signaling Cascades in Human Eosinophils
title_sort anti-allergic inflammatory activity of interleukin-37 is mediated by novel signaling cascades in human eosinophils
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023969/
https://www.ncbi.nlm.nih.gov/pubmed/29988381
http://dx.doi.org/10.3389/fimmu.2018.01445
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