ArticleBiochemical genetics2025
IRF4 Knockdown Inhibits the Chronic Rhinosinusitis Without Nasal Polyps Development by Regulating NLRP3/Caspase-1/GSDMD-Mediated Pyroptosis.
Article in Biochemical genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed, 4 citations in OpenAlex.
- GSDMD/Caspase-1-based evaluation of dydrogesterone in preventing recurrence after hysteroscopic endometrial polypectomy.Clinics (Sao Paulo, Brazil) · 2026Article
- Programmed Cell Death in Chronic Rhinosinusitis.Clinical and translational allergy · 2026Review
- Advances in the research of gasdermin-dependent pyroptosis mechanisms and therapeutic targets in inflammatory diseases.Apoptosis : an international journal on programmed cell death · 2026Review
- Monocyte/macrophage-derived NLRP3 Promotes the Onset and Progression of Ankylosing Spondylitis Via the NOD-like Receptor Pathway.Journal of clinical immunology · 2025Article
- Identification of immune-associated biomarkers in diagnosing allergic rhinitis.The World Allergy Organization journal · 2025Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic rhinosinusitis without nasal polyps (CRSsNP) is a CRS phenotype. However, the mechanisms of CRSsNP remains unclear. Differentially expressed genes (DEGs) were obtained from the GSE36830 and GSE198950 datasets through the GEO2R tool. The six hub genes were screened by the protein-protein interaction (PPI) network analysis and Cytoscape software. Then we constructed the mouse models of CRS and verified the expression levels of hub genes by reverse transcription quantitative PCR (RT-qPCR). Hematoxylin-eosin (HE) staining was employed to observe pathological alterations in mouse tissues. Casepase-3 expression was detected by immunohistochemistry (IHC). The levels of TNF-α, IL-12, IL-6, IL-1β, LDH, and IL-18 were evaluated using enzyme-linked immunosorbent assay (ELISA). Pyroptosis-related protein expressions were measured by western blotting. Cell counting kit-8 (CCK-8) and flow cytometry were performed to assess the proliferation and apoptosis of lipopolysaccharide (LPS)-induced NP69 cells. Six hub DEGs were identified. The expression levels of IRF4, IKZF1, and CD79A were obviously increased in CRSsNP, while those of ADH6, ADH1A, and LDHC were significantly decreased. IRF4 knockdown attenuated the pathologic features of CRSsNP. IRF4 knockdown reduced levels of the TNF-α, IL-12, IL-6 IL-1β, LDH, and IL-18 as well as the proteins expression of Casepase-1, GSDMD, and NLRP3 both in vivo and in vitro, implying that inflammation and pyroptosis were inhibited. IRF4 knockdown hinders the development of CRSsNP by inhibiting the inflammatory response and NLRP3/Caspase-1/GSDMD-mediated pyroptosis, which offers novel promising treatment strategies for clinical intervention.
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