Narirutin downregulates USP15 to inhibit the NLRP3 ubiquitination in HDM-induced allergic rhinitis.

BACKGROUND

Although tremendous progress has been made, the challenge of preventing and treating allergic rhinitis remains on a global scale. In recent years, there has been an increasing interest in the use of natural medicines. Narirutin, as a natural medicine, plays a significant role in anti - inflammation and anti - allergy. USP15, as an important member of the deubiquitinating enzyme family, can deubiquitinate NLRP3, thereby promoting the occurrence of allergic rhinitis.

PURPOSE

This study mainly investigated the mechanism of Narirutin inhibiting USP15 deubiquitination of NLRP3 and alleviating allergic rhinitis.

METHODS

In this study, the mechanism of Narirutin regulating USP15 deubiquitination of NLRP3 in vitro was investigated by molecular docking, Western blot, RT-qPCR, immunofluorescence, co-immunoprecipitation and other experimental methods. In vivo experiments, the AR mouse models were constructed using HDM induction, the nose touching and sneezing of AR mice were recorded. The mechanism of Narirutin alleviate the symptoms of allergic rhinitis in mice was studied by flow cytometry, HE, PAS, Western blot and other experimental methods.

RESULTS

The results showed that Narirutin inhibited the expression of NLRP3 by downregulating USP15 in RAW264.7 macrophages. Narirutin inhibits K63-linked ubiquitination of NLRP3 by decreasing USP15 in HEK293T cells. Importantly, siUSP15 alleviates mitochondrial damage in HNEpCs. In vivo experiments, it was further confirmed that Narirutin alleviated allergic rhinitis induced by HDM. After treatment with Narirutin, the symptoms of AR in mice were alleviated.

CONCLUSION

This study confirmed that Narirutin can alleviate AR by inhibiting USP15 deubiquitination of NLRP3, providing a new direction for the treatment and prevention of AR.