Activation of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome received substantial attention recently in inflammatory diseases. Macrophages contribute to allergic inflammation in asthma. The present study was aimed to investigate the effect of NLRP3 inflammasome on the polarization of macrophages. We utilized human primary monocytes and monocyte-derived macrophages to study the expression of NLRP3 inflammasome components (NLRP3, apoptosis-associated specklike protein, and caspase-1) and its downstream cytokine interleukin-1β (IL-1β). By gain- or loss-of-function assays, we next explored the effects of NLRP3 inflammasome on M1/M2 polarization and secretion of IL-4, interferon-γ, tumor necrosis factor-α, and IL-1β. The results showed increased numbers of M2 cells in asthma. And NLRP3 inflammasome was activated and involved in the inflammation of asthma. Furthermore, silence of NLRP3 down-regulated IL-4 secretion and up-regulated M1/M2. In contrast, overexpression of NLRP3 increased IL-4 and decreased M1/M2. As expected, IL-4 was involved in NLRP3-mediated down-regulation of Ml/M2 ratio. Moreover, NLRP3 interacted with IRF4 and was required for optimal IRF4-dependent IL-4 transcription. Subsequently, deficiency of NLRP3 in ovalbumin-induced allergic asthmatic mice impaired lung inflammation and up-regulated M1/M2, and diminished IL-4 in bronchoalveolar lavage fluid. Collectively, we demonstrated here that activation of NLRP3 was engaged in the promotion of asthma. NLRP3, but not the inflammasome adaptor ASC or caspase-1, promoted the polarization of M2 macrophages through up-regulating the expression of IL-4, thereby contributing to its regulation of asthma.
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June 2018
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A digital illustration of lung cancer cells. In this issue of the Biochemical Journal, Windhorst et al. investigate the effect of the actin- and calcium-regulating activities of ITPKB on the metastatic potential of lung cancer cells; for details, see pages 2057–2071.
Research Article|
June 21 2018
NLRP3 regulates macrophage M2 polarization through up-regulation of IL-4 in asthma
Ying Liu;
1Department of Respiration, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
Correspondence: Ying Liu (yingliu622@sina.com)
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Xin Gao;
Xin Gao
1Department of Respiration, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
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Yi Miao;
Yi Miao
1Department of Respiration, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
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Yuanyuan Wang;
Yuanyuan Wang
1Department of Respiration, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
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Huan Wang;
Huan Wang
1Department of Respiration, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
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Zhe Cheng;
Zhe Cheng
1Department of Respiration, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
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Xi Wang;
Xi Wang
1Department of Respiration, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
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Xiaogang Jing;
Xiaogang Jing
1Department of Respiration, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
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Liuqun Jia;
Liuqun Jia
1Department of Respiration, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
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Lingling Dai;
Lingling Dai
1Department of Respiration, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
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Meng Liu;
Meng Liu
1Department of Respiration, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
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Lin An
Lin An
1Department of Respiration, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
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Publisher: Portland Press Ltd
Received:
January 30 2018
Revision Received:
April 03 2018
Accepted:
April 06 2018
Accepted Manuscript online:
April 06 2018
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Biochem J (2018) 475 (12): 1995–2008.
Article history
Received:
January 30 2018
Revision Received:
April 03 2018
Accepted:
April 06 2018
Accepted Manuscript online:
April 06 2018
Citation
Ying Liu, Xin Gao, Yi Miao, Yuanyuan Wang, Huan Wang, Zhe Cheng, Xi Wang, Xiaogang Jing, Liuqun Jia, Lingling Dai, Meng Liu, Lin An; NLRP3 regulates macrophage M2 polarization through up-regulation of IL-4 in asthma. Biochem J 29 June 2018; 475 (12): 1995–2008. doi: https://doi.org/10.1042/BCJ20180086
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