Understanding the role of NLRP3-mediated pyroptosis in allergic rhinitis: A review

Cheng, Ning; Wang, Yunxiu; Gu, Zhifeng

doi:10.1016/j.biopha.2023.115203

Cited by 10 publications

(3 citation statements)

References 114 publications

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“…The NLRP3 inflammasome signaling pathway can be initiated by Toll-like receptors (TLRs); this initial step is followed by increases in cytokine production, activation of the nuclear factor-κB (NF-κB) signaling pathway to drive the transcription of NLRP3 receptor proteins and proinflammatory genes, activation of the adaptor protein ASC, formation of inflammasomes, and activation of Caspase-1, which promotes the release of several proinflammatory factors, including IL-1β and IL-18, and causes cellular pyroptosis [ 49 , 50 ]. The release of inflammatory factors leads to the development of an amplified inflammatory cascade response, which ultimately promotes the onset and progression of AR [ 51 ]. Moreover, previous studies showed that NLRP3 inflammasomes were significantly overexpressed in the nasal mucosal epithelium of AR patients, and the exacerbation of AR may be related to NLRP3-mediated nasal mucosal epithelial cellular pyroptosis [ 48 , 52 ].…”

Section: Discussionmentioning

confidence: 99%

Mechanistic study of acupuncture on the pterygopalatine ganglion to improve allergic rhinitis: analysis of multi-target effects based on bioinformatics/network topology strategie

Tian,

Sun,

Mao

et al. 2024

Briefings in Bioinformatics

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One of the prevalent chronic inflammatory disorders of the nasal mucosa, allergic rhinitis (AR) has become more widespread in recent years. Acupuncture pterygopalatine ganglion (aPPG) is an emerging alternative therapy that is used to treat AR, but the molecular mechanisms underlying its anti-inflammatory effects are unclear. This work methodically demonstrated the multi-target mechanisms of aPPG in treating AR based on bioinformatics/topology using techniques including text mining, bioinformatics, and network topology, among others. A total of 16 active biomarkers and 108 protein targets related to aPPG treatment of AR were obtained. A total of 345 Gene Ontology terms related to aPPG of AR were identified, and 135 pathways were screened based on Kyoto Encyclopedia of Genes and Genomes analysis. Our study revealed for the first time the multi-targeted mechanism of action of aPPG in the treatment of AR. In animal experiments, aPPG ameliorated rhinitis symptoms in OVA-induced AR rats; decreased serum immunoglobulin E, OVA-sIgE, and substance P levels; elevated serum neuropeptide Y levels; and modulated serum Th1/Th2/Treg/Th17 cytokine expression by a mechanism that may be related to the inhibition of activation of the TLR4/NF-κB/NLRP3 signaling pathway. In vivo animal experiments once again validated the results of the bioinformatics analysis. This study revealed a possible multi-target mechanism of action between aPPG and AR, provided new insights into the potential pathogenesis of AR, and proved that aPPG was a promising complementary alternative therapy for the treatment of AR.

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Section: Discussionmentioning

confidence: 99%

Mechanistic study of acupuncture on the pterygopalatine ganglion to improve allergic rhinitis: analysis of multi-target effects based on bioinformatics/network topology strategie

Tian,

Sun,

Mao

et al. 2024

Briefings in Bioinformatics

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“…Furthermore, macrophages, known for their diverse roles in immunity, have been implicated in allergic conditions 9 . Studies have explored the involvement of macrophage pyroptosis—a form of inflammatory cell death—in exacerbating allergic responses, with the release of pro‐inflammatory cytokines amplifying the immune cascade 10,11 …”

Section: Introductionmentioning

confidence: 99%

“…The emerging role of the NLRP3 inflammasome pathway in allergic diseases has garnered attention. Investigations suggest its involvement in modulating immune responses, influencing the balance between Th1 and Th2 cells, and exacerbating allergic reactions 10,12,13 . Additionally, studies investigating the contributions of innate immune receptors, such as NLRP3, in AR have revealed potential therapeutic targets for immune modulation.…”

Section: Introductionmentioning

confidence: 99%

Immunomodulation in allergic rhinitis: Insights from Th2 cells and NLRP3/IL‐18 pathway

Hu,

Liu,

Jing

et al. 2024

Cell Biochemistry & Function

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Allergic rhinitis (AR) is characterized by nasal symptoms such as rubbing and sneezing, often triggered by allergen exposure. The purpose of this study is to dissect the roles of NLRP3‐mediated immune modulation and macrophage pyroptosis in modulating T cell differentiation within the context of ovalbumin (OVA)‐induced AR in mice. OVA‐induced AR was established in mice, evaluating nasal symptoms, macrophage infiltration, cytokine levels, and T cell differentiation. Manipulations using NLRP3−/−, ASC−/− mice, clodronate liposome treatment, and NLRP3 inhibitor MCC950 were performed to assess their impact on AR symptoms and immune responses. Following OVA stimulation, increased nasal symptoms were observed in the OVA group along with augmented GATA3 expression and elevated IL‐4 and IL‐1b levels, indicative of Th2 polarization and cellular pyroptosis involvement. NLRP3−/− and ASC−/− mice exhibited reduced CD3+ T cells post OVA induction, implicating cellular pyroptosis in AR. Macrophage depletion led to decreased IgE levels, highlighting their involvement in allergic responses. Further investigations revealed enhanced macrophage pyroptosis, influencing Th1/Th2 differentiation in AR models. IL‐18 released through NLRP3‐mediated pyroptosis induced Th2 differentiation, distinct from IL‐1b. Additionally, MCC950 effectively mitigated AR symptoms by modulating Th2 responses and reducing macrophage infiltration. This comprehensive study unravels the pivotal role of NLRP3‐mediated immune modulation and macrophage pyroptosis in Th1/Th2 balance regulation in OVA‐induced AR. Targeting NLRP3 pathways with MCC950 emerged as a promising strategy to alleviate AR symptoms, providing insights for potential therapeutic interventions in AR management.

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Hypersensitivity Reactions in the Respiratory Tract

Burleson,

Johnson

2024

Reference Module in Biomedical Sciences

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Understanding the role of NLRP3-mediated pyroptosis in allergic rhinitis: A review

Cited by 10 publications

References 114 publications

Mechanistic study of acupuncture on the pterygopalatine ganglion to improve allergic rhinitis: analysis of multi-target effects based on bioinformatics/network topology strategie

Mechanistic study of acupuncture on the pterygopalatine ganglion to improve allergic rhinitis: analysis of multi-target effects based on bioinformatics/network topology strategie

Immunomodulation in allergic rhinitis: Insights from Th2 cells and NLRP3/IL‐18 pathway

Hypersensitivity Reactions in the Respiratory Tract

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