TLR4 antagonist ameliorates combined allergic rhinitis and asthma syndrome (CARAS) by reducing inflammatory monocytes infiltration in mice model
TLR4 antagonist ameliorates combined allergic rhinitis and asthma syndrome (CARAS) by reducing inflammatory monocytes infiltration in mice model
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DOI：
10.1016/j.intimp.2019.05.021
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发表时间：
2019-08-01
影响因子：
5.6
通讯作者：
Sun, Jie
中科院分区：
文献类型：
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作者：
Tang, Huaping;Li, Tingtian;Sun, Jie
本研究旨在探讨Toll样受体4（TLR 4）拮抗剂对卵清蛋白（OVA）诱导的小鼠变应性鼻炎和哮喘综合征（卡拉斯）模型的影响。建立了OVA诱导的卡拉斯小鼠模型，并鼻内或腹腔内给予TLR 4拮抗剂TAK-242。计算打喷嚏和擦鼻次数。采用流式细胞术分析支气管肺泡灌洗液（BALF）和鼻灌洗液（NLF）中不同类型细胞的频率。免疫印迹法检测鼻黏膜和肺组织蛋白表达。采用酶联免疫吸附试验（ELISA）测定白细胞介素（IL）-4，IL-5和IL-13的水平。应用组织学评分评估肺损伤。TAK-242治疗下调了CCL 2表达，并减少了鼻粘膜和肺组织中的单核细胞浸润。此外，TAK-242治疗通过调节细胞因子（包括IL-4、IL-5和IL-13）改善了上呼吸道症状（包括打喷嚏和擦鼻）。此外，TAK-242治疗可改善下呼吸道症状，包括降低BALF中CD 45（+）SiglecF（+）CD 11b（+）CD 11 c（-）嗜酸性粒细胞和肺中IL 13（+）Th 2细胞的频率。总之，TAK-242治疗通过抑制淋巴细胞浸润、减少单核细胞浸润以及调节嗜酸性粒细胞和Th 2细胞的频率来改善CARAS相关肺损伤。
The present study aims to investigate the effects of toll-like receptor 4 (TLR4) antagonist in an ovalbumin (OVA)-induced mouse model of combined allergic rhinitis and asthma syndrome (CARAS). An OVA-induced mouse model of CARAS was established and TLR4 antagonist, TAK-242, was administrated intranasally or intraperitoneally. The number of sneezing and nasal rubbing was counted. The frequency of different cell types in the bronchoalveolar lavage fluid (BALF) and nasal lavage fluid (NLF) was analyzed using flow cytometry. Expressions of protein in nasal mucosa and lungs were determined using western blotting. Levels of interleukin (IL)-4, IL-5, and IL-13 were determined using Enzyme-linked Immunosorbent Assay (ELISA). Histological scores were applied for the assessment of lung injury. Treatment of TAK-242 downregulated CCL2 expression and reduced monocyte infiltration in nasal mucosa and lung tissues. Additionally, treatment of TAK-242 ameliorated upper airway symptoms including the sneezing and nasal rubbing by the regulation of cytokines including IL-4, IL-5, and IL-13. Furthermore, treatment of TAK-242 ameliorated lower airway symptoms including decreasing the frequency of CD45(+)SiglecF(+)CD11b(+)CD11c(-) eosinophils in BALF and IL13(+) Th2 cells in the lungs. In conclusion, treatment of TAK-242 ameliorated CARAS-related lung injury by inhibiting lymphocyte infiltration, reducing monocytes infiltration, as well as regulating the frequency of eosinophils and Th2 cells.