Department of Otolaryngology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
Department of Rehabilitation Medicine, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Immun Inflamm Dis. 2023 Sep;11(9):e1002. doi: 10.1002/iid3.1002.
Allergic rhinitis (AR) is a common allergic disorder, afflicting thousands of human beings. Aberrant mitochondrial dynamics are important pathological elements for various immune cell dysfunctions and allergic diseases. However, the connection between mitochondrial dynamics and AR remains poorly understood. This study aimed to determine whether mitochondrial dynamics influence the inflammatory response in AR.
In the present study, we established a murine model of AR by sensitization with ovalbumin (OVA). Then, we investigated the mitochondrial morphology in mice with AR by transmission electron microscopy and confocal fluorescence microscopy, and evaluated the role of Mdivi-1 (an inhibitor of mitochondrial fission) on allergic symptoms, inflammatory responses, allergic-related signals, and reactive oxygen species formation.
There was a notable enhancement in mitochondrial fragmentation in the nasal mucosa of mice following OVA stimulation, whereas Mdivi-1 prevented aberrant mitochondrial morphology. Indeed, Mdivi-1 alleviated the rubbing and sneezing responses in OVA-sensitized mice. Compared with vehicle-treated ones, mice treated with Mdivi-1 exhibited a reduction in interleukin (IL)-4, IL-5, and specific IgE levels in both serum and nasal lavage fluid, and shown an amelioration in inflammatory response of nasal mucosa. Meanwhile, Mdivi-1 treatment was associated with a suppression in JAK2 and STAT6 activation and reactive oxygen species generation, which act as important signaling for allergic response.
Our findings reveal mitochondrial dynamics modulate the allergic responses in AR. Mitochondrial dynamics may represent a promising target for the treatment of AR.
变应性鼻炎（AR）是一种常见的过敏性疾病，影响着成千上万的人类。线粒体动力学异常是各种免疫细胞功能障碍和过敏性疾病的重要病理因素。然而，线粒体动力学与 AR 之间的联系仍知之甚少。本研究旨在确定线粒体动力学是否会影响 AR 中的炎症反应。
在本研究中，我们通过卵清蛋白（OVA）致敏建立了 AR 小鼠模型。然后，我们通过透射电子显微镜和共聚焦荧光显微镜观察 AR 小鼠的线粒体形态，并评估 Mdivi-1（一种线粒体分裂抑制剂）对过敏症状、炎症反应、过敏相关信号和活性氧形成的作用。
OVA 刺激后，小鼠鼻黏膜中线粒体明显碎片化，而 Mdivi-1 可防止异常线粒体形态。事实上，Mdivi-1 可减轻 OVA 致敏小鼠的搔抓和打喷嚏反应。与对照组相比，Mdivi-1 治疗组的血清和鼻洗液中白细胞介素（IL）-4、IL-5 和特异性 IgE 水平降低，鼻黏膜炎症反应减轻。同时，Mdivi-1 治疗可抑制 JAK2 和 STAT6 的激活以及活性氧的产生，这些信号转导对于过敏反应至关重要。
我们的研究结果表明，线粒体动力学调节 AR 中的过敏反应。线粒体动力学可能成为 AR 治疗的一个有前途的靶点。
