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
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.
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P2X7 receptor expression deletion appears to be beneficial in acute lung injury, asthma, lung inflammation, and fibrosis.
“In addition, P2X7 receptor expression deletion appears to be beneficial in case of acute lung injury, asthma, lung inflammation, and fibrosis [87–91].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [91]
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- Authors
- Li, R., Wang, J., Li, R., Zhu, F., Xu, W., Zha, G., He, G., Cao, H., Wang, Y., & Yang, J.
- Affiliations
- Zhongnan Hospital of Wuhan University (CN)
- Renmin Hospital of Wuhan University (CN)
- Corresponding author
- Yang, Jiong
- Venue
- Experimental Cell Research
- Publisher
- Elsevier BV
- Published
- 2018-05
- Volume
- 366
- Issue
- 1
- Pages
- 1-15
- ISSN
- 0014-4827 (ISSN-L)
- OpenAlex
- W2792275498
- Cited by
- 68
- References
- 64
- Citations by year
- 2026: 6 · 2025: 18 · 2024: 9 · 2023: 9 · 2022: 9 · 2021: 7 · 2020: 8 · 2019: 2
- FWCI
- 3.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Cell Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81670024)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- asthma, dendritic cells, NLRP3 inflammasome, HMGB1, airway hyperresponsiveness, airway inflammation, Th2 polarization, Th17 polarization, IL-1β, IL-18, ovalbumin-induced asthma, purinergic signaling
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Adenosine Triphosphate, Animals, Asthma, Cell Differentiation, Dendritic Cells, Female, Lung, Male, Mice, Inbred C57BL, Pneumonia, Th2 Cells, HMGB1 Protein, Mice, Receptors, Purinergic P2X7, Th17 Cells, Inflammasomes
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