Acupuncture alleviates asthma inflammation in mice by upregulating miR-223, suppressing NLRP3 pyroptosis pathway

Allergic asthma is a chronic inflammatory airway disease characterized by airway hyperresponsiveness and remodeling. While acupuncture has shown promise as a complementary therapy, its precise molecular mechanisms remain largely undefined. A critical gap exists in understanding how acupuncture modulates cellular processes like pyroptosis, a highly inflammatory form of programmed cell death, which is increasingly implicated in asthma pathogenesis. Current treatments often target symptoms, but a deeper mechanistic understanding could unlock novel therapeutic strategies by modulating specific inflammatory pathways.

Researchers established OVA-induced asthma in wild-type and NLRP3-/- C57BL mice, and lipopolysaccharide (LPS)-induced inflammation in 16HBE human bronchial epithelial cells for in vivo and in vitro studies. The acupuncture intervention involved specific treatment protocols applied to the asthmatic mice. Various techniques were employed to assess inflammation and pyroptosis, including H&E, Masson, and Sirius staining for tissue pathology, ELISA for cytokine levels, Western Blot and PCR for gene and protein expression, LDH assay for cell death, and immunohistochemistry and immunofluorescence for protein localization. A dual-luciferase assay was used to confirm direct gene interaction.

In asthmatic mice, acupuncture treatment significantly alleviated airway inflammation. This therapeutic effect was associated with a notable upregulation of miR-223 expression. Concurrently, acupuncture inhibited the expression levels of key genes and proteins within the NLRP3 pathway, including NLRP3, GSDMD, ASC, and Caspase-1, all central to pyroptosis. Furthermore, acupuncture lowered the presence of cytokines associated with T cells, indicating a broader immunomodulatory effect. Activation of the NLRP3 pathway was observed to exacerbate asthma symptoms, reinforcing its pathogenic role. In vitro, modulating miR-223 expression in LPS-induced cell inflammation models significantly altered NLRP3 pathway component levels. > The dual-luciferase assay provided direct evidence that miR-223-3p specifically binds to the NLRP3 gene, thereby suppressing its transcriptional activity and subsequent protein expression.