Abstract：
Allergic rhinitis is a common non-infectious inflammatory disease that affects approximately 15 % of people worldwide and has a complex and unclear aetiology. In recent years, pyroptosis has been found to play a role in the development of allergic rhinitis. IL-9, pyroptosis, serum and glucocorticoid-induced protein kinase 1 (SGK1), NOD-like receptor 3 (NLRP3), and nuclear factor kappa B (NF-κB) have been shown to influence each other. Herein, we aimed to explore the role of IL-9 neutralising antibody in pyroptosis involving IL-9, SGK1, NF-κB, and NLRP3 in allergic rhinitis. We observed a decrease in cytokines involved in pyroptosis and gasdermin D (GSDMD) compared with those in mice with allergic rhinitis. Further, phosphorylation of NF-κB/p65 decreased compared with that in mice with allergic rhinitis; NLRP3 and ASC also decreased, although the levels were higher than those in controls. SGK1 levels decreased compared with that in mice with allergic rhinitis and increased after using IL-9 neutralising antibodies, thus demonstrating its negative regulatory effects. The IL-9 neutralising antibody reduced the inflammatory and pyroptosis responses via SGK1 and NF-κB/NLRP3/GSDMD pathway. Our research results indicate that IL-9 regulates allergic rhinitis via the influence of SGK1 and NF-κB/NLRP3/GSDMD signalling pathway, providing new insights for developing novel drugs to treat allergic rhinitis.
摘要：
变应性鼻炎是一种常见的非感染性炎性疾病，影响全球约15％的人，病因复杂且不清楚。近年来,已发现焦亡在变应性鼻炎的发展中起作用。IL-9，焦亡，血清和糖皮质激素诱导的蛋白激酶1（SGK1），NOD样受体3(NLRP3),和核因子κB（NF-κB）已被证明是相互影响的。在这里，我们旨在探讨IL-9中和抗体在涉及IL-9、SGK1、NF-κB、和NLRP3在过敏性鼻炎中。与过敏性鼻炎小鼠相比，我们观察到与焦亡和gasderminD（GSDMD）有关的细胞因子减少。Further,与变应性鼻炎小鼠相比,NF-κB/p65磷酸化水平降低;NLRP3和ASC,尽管水平高于对照组。SGK1水平与过敏性鼻炎小鼠相比降低，使用IL-9中和抗体后升高，从而证明了它的负面调节作用。IL-9中和抗体通过SGK1和NF-κB/NLRP3/GSDMD途径降低了炎症和焦亡反应。我们的研究结果表明，IL-9通过SGK1和NF-κB/NLRP3/GSDMD信号通路的影响调节变应性鼻炎，为开发治疗过敏性鼻炎的新药提供新的见解。
