AIM2 inflammasome activation may mediate high mobility group box 1 release in murine allergic rhinitis

Abstract Introduction: High mobility group box 1 protein participates in the pathogenesis of allergic rhinitis. Activation of the inflammasome can mediate the release of high mobility group box 1. The role of the absent in melanoma 2 inflammasome in allergic rhinitis remains unclear. Objective: This study aimed to investigate the function of absent in melanoma 2 inflammasome in murine allergic rhinitis and the interaction between high mobility group box 1 and the absent in melanoma 2 inflammasome. Methods: A murine allergic rhinitis model was established using twenty Balb/c mice. Expression of the components of the absent in melanoma 2 inflammasome: absent in melanoma 2, apoptosis-associated speck-like protein containing a CARD (Asc), caspase-1 p20, and additional nod-like receptor family pyrin domain containing 3 (Nlrp3) were detected by western blotting during allergic rhinitis. Alterations of absent in melanoma 2, caspase-1, and high mobility group box 1 after ovalbumin challenge were demonstrated by immunohistochemistry. TdT-mediated dUTP Nick end labeling, TUNEL assay, and cleavage of caspase-3 and PARP-1 were used for the observation of pyroptosis. Results: Eosinophilia and goblet cell infiltration were observed in the nasal mucosa of mice in the allergic rhinitis group. Absent in melanoma 2, Asc, and caspase-1 p20 increased after ovalbumin exposure while Nlrp3 did not. High mobility group box 1 was released in the nasal mucosa of allergic rhinitis mice. TUNEL-positive cells increased in the epithelium and laminae propria, whereas cleavage of caspase-3 and PARP-1 was not observed. Conclusions: The absent in melanoma 2 inflammasome was activated and pyroptosis may occur in the nasal mucosa after ovalbumin treatment. These may contribute to the translocation of high mobility group box 1 and the development of allergic rhinitis.

摘要与引言：高迁移率族蛋白B1（high mobility group box 1 protein）参与变应性鼻炎的发病机制。炎性体（inflammasome）的激活可介导高迁移率族蛋白B1的释放。目前黑素瘤缺失2（absent in melanoma 2，AIM2）炎性体在变应性鼻炎中的作用仍不明确。
研究目的：本研究旨在探讨黑素瘤缺失2炎性体在小鼠变应性鼻炎中的作用，以及高迁移率族蛋白B1与黑素瘤缺失2炎性体之间的相互作用。
实验方法：本研究选用20只BALB/c小鼠构建小鼠变应性鼻炎模型。在变应性鼻炎造模期间，通过蛋白质印迹法（Western blotting）检测黑素瘤缺失2炎性体的组分表达：黑素瘤缺失2、含半胱天冬酶激活域的凋亡相关斑点样蛋白（apoptosis-associated speck-like protein containing a CARD，Asc）、半胱天冬酶-1 p20，以及另外的核苷酸结合寡聚化结构域样受体蛋白3（nod-like receptor family pyrin domain containing 3，NLRP3）。通过免疫组织化学法观察卵清蛋白（ovalbumin）激发后黑素瘤缺失2、半胱天冬酶-1及高迁移率族蛋白B1的表达变化。采用脱氧核糖核苷酸末端转移酶介导的dUTP缺口末端标记（TUNEL）实验、半胱天冬酶-3与多聚ADP核糖聚合酶-1（PARP-1）的剪切情况观察焦亡（pyroptosis）现象。
实验结果：变应性鼻炎组小鼠鼻黏膜可见嗜酸性粒细胞浸润及杯状细胞浸润。卵清蛋白激发后，黑素瘤缺失2、Asc及半胱天冬酶-1 p20的表达均上调，而NLRP3无明显变化。变应性鼻炎小鼠鼻黏膜中可检测到高迁移率族蛋白B1的释放。上皮层及固有层中TUNEL阳性细胞数量增加，但未观察到半胱天冬酶-3与PARP-1的剪切现象。
结论：卵清蛋白激发后，黑素瘤缺失2炎性体被激活，鼻黏膜可能发生焦亡。上述变化可能参与高迁移率族蛋白B1的转位过程，并促进变应性鼻炎的发生发展。