Aryl hydrocarbon receptor negatively regulates NLRP3 inflammasome activity by inhibiting NLRP3 transcription
Open accessAbstract
NLRP3 inflammasome is a multi-protein complex, which plays crucial roles in host defense against pathogens. The NLRP3 protein level is considered rate limiting for the activation of the inflammasome, thus its expression must be tightly controlled to maintain immune homeostasis. However, the molecular mechanisms that modulate NLRP3 expression, especially at the transcriptional level, remain largely unknown. In the present study, we show that aryl hydrocarbon receptor (AhR) activation inhibits NLRP3 expression, caspase-1 activation and subsequent IL-1β secretion in peritoneal macrophages, whereas siRNA knockdown of AhR has opposite effects. AhR could bind to the xenobiotic response element (XRE) in the NLRP3 promoter and inhibit NLRP3 transcription. Furthermore, AhR activation suppresses Alum-induced peritonitis in vivo. Therefore, we identified AhR as a negative regulator of NLRP3 inflammasome activity by inhibiting the transcription of NLRP3 and suggested AhR as a potential target for the intervention of diseases with uncontrolled inflammasome activation.
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The aryl hydrocarbon receptor (AhR) has been shown to negatively regulate NLRP3 inflammasome activity.
“The aryl hydrocarbon receptor (AhR) has been shown to negatively regulate NLRP3 inflammasome activity (21).”
From Sepsis-Induced Gut Dysbiosis Mediates the Susceptibility to Sepsis-Associated Encephalopathy in Mice (2022) · cites this paper as [21]
AhR is a negative regulator of NLRP3 inflammasome activity at the transcriptional level.
“In addition, AhR was shown to be a negative regulator of NLRP3 inflammasome activity at the transcriptional level (21).”
From Sepsis-Induced Gut Dysbiosis Mediates the Susceptibility to Sepsis-Associated Encephalopathy in Mice (2022) · cites this paper as [21]
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“The aryl hydrocarbon receptor (AhR) has been shown to negatively regulate NLRP3 inflammasome activity (21).”
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- Authors
- Huai, W., Zhao, R., Song, H., Zhao, J., Zhang, L., Zhang, L., Gao, C., Han, L., & Zhao, W.
- Affiliations
- Shandong University (CN)
- Second Military Medical University (CN)
- Corresponding author
- Han, Lihui
- Zhao, Wei
- ORCID
- Venue
- Nature Communications
- Published
- 2014-08-20
- Volume
- 5
- Issue
- 1
- Pages
- 4738-4738
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2073875167
- Cited by
- 211
- References
- 53
- Citations by year
- 2026: 17 · 2025: 17 · 2024: 25 · 2023: 14 · 2022: 19 · 2021: 27 · 2020: 26 · 2019: 15 · 2018: 16 · 2017: 20 · 2016: 9 · 2015: 6
- FWCI
- 4.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Shandong University
- National Natural Science Foundation of China (81172352, 31000407, 81000495, 31370017)
- Natural Science Foundation of Shandong Province (ZR2011CQ001)
- Independent Innovation Foundation of Shandong University (2012TS122)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Keywords
- aryl hydrocarbon receptor, NLRP3 inflammasome, xenobiotic response element, caspase-1 activation, IL-1β secretion, peritoneal macrophages, immune homeostasis, negative regulation of inflammation
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Alum Compounds, Animals, Carrier Proteins, Dimethyl Sulfoxide, Female, Gene Expression Regulation, Mice, Inbred C57BL, Peritonitis, Protein Binding, Transcription, Genetic, Signal Transduction, Macrophages, Peritoneal, Receptors, Aryl Hydrocarbon, Caspase 1, Response Elements, RNA, Small Interfering, Mice, Interleukin-1beta, Inflammasomes, Primary Cell Culture
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