Department of Otorhinolaryngology Head and Neck Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266000, PR China.
Department of Otorhinolaryngology Head and Neck Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266000, PR China.
Int Immunopharmacol. 2020 Sep;86:106522. doi: 10.1016/j.intimp.2020.106522. Epub 2020 Jun 22.
Allergic rhinitis (AR) is a common chronic condition characterized by inflammation of the nasal mucosa. The correlation of microRNAs (miRNAs) in AR has been highlighted particularly due to their roles in regulating inflammatory responses. The aim of this study was to explore the anti-inflammatory mechanism by which miR-345-5p regulates the toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) pathway in mice with AR. Initially, the putative miR-345-5p binding sites on the 3'untranslated region of TLR4 was predicted and verified. AR models were established using ovalbumin, after which the functional role of miR-345-5p in AR was determined using gain- and loss-of-function approaches. We found that miR-345-5p was poorly expressed in nasal mucosal tissues of mice with AR. Meanwhile, TLR4 expression and the TLR4/NF-κB pathway were identified to be promoted, which were then suppressed in the presence of overexpressed miR-345-5p. In addition, nasal epithelial cell apoptosis and fibrosis were inhibited in response to miR-345-5p overexpression and TLR4 silencing. Furthermore, miR-345-5p overexpression and TLR4 silencing were observed to decrease Th2 cells, expression of pro-inflammatory factors, but to increase Th1 cells and expression of anti-inflammatory factors. This study demonstrates an important role of miR-345-5p in alleviating the inflammatory response in mice with AR by inhibiting the TLR4/NF-κB pathway. Therefore, a better understanding of this process may aid in the development of novel therapeutic agents of AR.
变应性鼻炎(AR)是一种常见的慢性疾病,其特征为鼻黏膜炎症。由于 microRNAs(miRNAs)在调节炎症反应中的作用,AR 中的 miRNAs 相关性备受关注。本研究旨在探讨 miR-345-5p 通过调节 TLR4/NF-κB 通路在 AR 小鼠中发挥抗炎作用的机制。首先,预测并验证了 TLR4 3'非翻译区(UTR)上 miR-345-5p 的假定结合位点。使用卵清蛋白建立 AR 模型,然后通过功能获得和功能丧失方法确定 miR-345-5p 在 AR 中的作用。结果发现,AR 小鼠鼻黏膜组织中 miR-345-5p 表达水平较低。同时,发现 TLR4 表达和 TLR4/NF-κB 通路被激活,而在过表达 miR-345-5p 时被抑制。此外,miR-345-5p 过表达和 TLR4 沉默抑制了鼻上皮细胞凋亡和纤维化。进一步研究发现,miR-345-5p 过表达和 TLR4 沉默可减少 Th2 细胞,降低促炎因子的表达,增加 Th1 细胞,提高抗炎因子的表达。综上所述,miR-345-5p 通过抑制 TLR4/NF-κB 通路缓解 AR 小鼠的炎症反应,因此,深入了解这一过程可能有助于开发新型 AR 治疗药物。