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Title: ATP/P2X7-NLRP3 axis of dendritic cells participates in the regulation of airway inflammation and hyper-responsiveness in asthma by mediating HMGB1 expression and secretion

Abstract

Highlights: • ATP/P2X7 axis induces Th2, 17 cell inflammatory response and AHR in allergic asthma. • Inhibiting NLRP3 blocks Th2, 17 cell inflammatory response and AHR in allergic asthma. • Activating ATP/P2X7 axis increases NLRP3 inflammasome complex expression. • Activating ATP/P2X7 axis induces HMGB1 expresssion and release from DCs. • Inhibiting NLRP3 reduces HMGB1 expresssion and release from DCs. The ATP/P2X7 axis of dendritic cells (DCs) mediates the activation of NLRP3 inflammasome and promotes secretion of interleukin (IL)−1β and IL-18 to induce T helper (Th) 2, Th17 differentiation in the pathogenesis of asthma. NLRP3 inflammasome also regulates high mobility protein 1 (HMGB1) release in DCs. Recent studies demonstrated the correlation between HMGB1 expression and airway inflammation and hyper-responsiveness (AHR) in asthma. However, the relationship between the ATP/P2X7-NLRP3 axis and HMGB1 in DCs in asthma is still unclear. ATP, apyrase, Brilliant Blue G, BzATP, glibenclamide, and Z-YVAD-FMK were administered to ovalbumin (OVA)-induced murine asthmatic model. For in vitro studies, bone marrow-derived mononuclear cells (BMDCs) were primed with LPS and stimulated with the same reagents. Activation of the ATP/P2X7 axis aggravated airway inflammation and AHR in the lung and induced Th2, Th17 polarization in asthmatic mice. Inhibition of NLRP3 inflammasome weakened cardinalmore » features of asthma and blocked Th2, Th17 polarization. In vitro and vivo, ATP/P2X7 axis activated NLRP3 inflammasome and induced HMGB1 expression and release from DCs. Inhibition of NLRP3 inflammasome reduced HMGB1 expression and release. The ATP/P2X7-NLRP3 axis of DCs participates in mediating airway inflammation, AHR, and promoting Th2, Th17 inflammatory responses in asthmatic mice by inducing HMGB1 expression and secretion.« less

Authors:
 [1];  [2];  [3];  [2];  [1];  [4]; ; ; ;  [1]
  1. Department of Respiratory Medicine, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, Hubei 430071 (China)
  2. Department of Intensive Care Unit, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071 (China)
  3. Department of Neurology, Hubei third people's Hospital, Wuhan, Hubei 430033 (China)
  4. Department of Respiratory Medicine, People's Hospital of Wuhan University, Wuhan, Hubei 430060 (China)
Publication Date:
OSTI Identifier:
23082400
Resource Type:
Journal Article
Journal Name:
Experimental Cell Research
Additional Journal Information:
Journal Volume: 366; Journal Issue: 1; Other Information: Copyright (c) 2018 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0014-4827
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ASTHMA; BONE MARROW; INFLAMMATION; LUNGS; LYMPHOKINES; MICE; OVALBUMIN

Citation Formats

Li, Ruiting, Wang, Jing, Li, Ruifang, Zhu, Fangfang, Xu, Wenjuan, Zha, Gan, He, Guangzhen, Cao, Huan, Wang, Yimin, and Yang, Jiong. ATP/P2X7-NLRP3 axis of dendritic cells participates in the regulation of airway inflammation and hyper-responsiveness in asthma by mediating HMGB1 expression and secretion. United States: N. p., 2018. Web. doi:10.1016/J.YEXCR.2018.03.002.
Li, Ruiting, Wang, Jing, Li, Ruifang, Zhu, Fangfang, Xu, Wenjuan, Zha, Gan, He, Guangzhen, Cao, Huan, Wang, Yimin, & Yang, Jiong. ATP/P2X7-NLRP3 axis of dendritic cells participates in the regulation of airway inflammation and hyper-responsiveness in asthma by mediating HMGB1 expression and secretion. United States. https://doi.org/10.1016/J.YEXCR.2018.03.002
Li, Ruiting, Wang, Jing, Li, Ruifang, Zhu, Fangfang, Xu, Wenjuan, Zha, Gan, He, Guangzhen, Cao, Huan, Wang, Yimin, and Yang, Jiong. 2018. "ATP/P2X7-NLRP3 axis of dendritic cells participates in the regulation of airway inflammation and hyper-responsiveness in asthma by mediating HMGB1 expression and secretion". United States. https://doi.org/10.1016/J.YEXCR.2018.03.002.
@article{osti_23082400,
title = {ATP/P2X7-NLRP3 axis of dendritic cells participates in the regulation of airway inflammation and hyper-responsiveness in asthma by mediating HMGB1 expression and secretion},
author = {Li, Ruiting and Wang, Jing and Li, Ruifang and Zhu, Fangfang and Xu, Wenjuan and Zha, Gan and He, Guangzhen and Cao, Huan and Wang, Yimin and Yang, Jiong},
abstractNote = {Highlights: • ATP/P2X7 axis induces Th2, 17 cell inflammatory response and AHR in allergic asthma. • Inhibiting NLRP3 blocks Th2, 17 cell inflammatory response and AHR in allergic asthma. • Activating ATP/P2X7 axis increases NLRP3 inflammasome complex expression. • Activating ATP/P2X7 axis induces HMGB1 expresssion and release from DCs. • Inhibiting NLRP3 reduces HMGB1 expresssion and release from DCs. The ATP/P2X7 axis of dendritic cells (DCs) mediates the activation of NLRP3 inflammasome and promotes secretion of interleukin (IL)−1β and IL-18 to induce T helper (Th) 2, Th17 differentiation in the pathogenesis of asthma. NLRP3 inflammasome also regulates high mobility protein 1 (HMGB1) release in DCs. Recent studies demonstrated the correlation between HMGB1 expression and airway inflammation and hyper-responsiveness (AHR) in asthma. However, the relationship between the ATP/P2X7-NLRP3 axis and HMGB1 in DCs in asthma is still unclear. ATP, apyrase, Brilliant Blue G, BzATP, glibenclamide, and Z-YVAD-FMK were administered to ovalbumin (OVA)-induced murine asthmatic model. For in vitro studies, bone marrow-derived mononuclear cells (BMDCs) were primed with LPS and stimulated with the same reagents. Activation of the ATP/P2X7 axis aggravated airway inflammation and AHR in the lung and induced Th2, Th17 polarization in asthmatic mice. Inhibition of NLRP3 inflammasome weakened cardinal features of asthma and blocked Th2, Th17 polarization. In vitro and vivo, ATP/P2X7 axis activated NLRP3 inflammasome and induced HMGB1 expression and release from DCs. Inhibition of NLRP3 inflammasome reduced HMGB1 expression and release. The ATP/P2X7-NLRP3 axis of DCs participates in mediating airway inflammation, AHR, and promoting Th2, Th17 inflammatory responses in asthmatic mice by inducing HMGB1 expression and secretion.},
doi = {10.1016/J.YEXCR.2018.03.002},
url = {https://www.osti.gov/biblio/23082400}, journal = {Experimental Cell Research},
issn = {0014-4827},
number = 1,
volume = 366,
place = {United States},
year = {Tue May 15 00:00:00 EDT 2018},
month = {Tue May 15 00:00:00 EDT 2018}
}