Zhang Yu-Lian, Han Doo Hee, Kim Dong-Young, Lee Chul Hee, Rhee Chae-Seo
Department of Otorhinolaryngology-head and Neck Surgery, Seoul National University College of Medicine, Seoul, Korea.
Research Center for Sensory Organs, and Institute of Allergy, Seoul, Korea.
PLoS One. 2017 Jan 3;12(1):e0169353. doi: 10.1371/journal.pone.0169353. eCollection 2017.
The proinflammatory cytokine interleukin (IL)-17A is associated with eosinophil infiltration into the nasal mucosa in a mouse model of ovalbumin-induced allergic rhinitis. Chemotaxis of eosinophils is mediated primarily through C-C chemokine receptor type 3 (CCR3). However, the mechanism underlying the IL-17A-mediated enhancement of eosinophil recruitment via chemoattractants/chemokines remains unknown.
In this study, we assessed the contribution of IL-17A to eosinophil-related inflammation via the CCL7/CCR3 pathway in experimental allergic rhinitis.
IL-17A knockout (KO) and wild-type (WT) BALB/c mice were injected intraperitoneally and challenged intranasally with OVA to induce allergic rhinitis. Various parameters of the allergic response were evaluated, and mRNA and protein levels of CCL7 and CCR3 in nasal tissue and serum were compared between the two groups. The chemotactic response to CCL7 with or without IL-17A in bone marrow-derived eosinophils (bmEos) from BALB/c mice was measured.
In the allergic rhinitis model, IL-17A deficiency significantly decreased nasal symptoms, serum IgE levels, and eosinophil recruitment to the nasal mucosa. CCL7 and CCR3 mRNA and protein levels were decreased in the nasal mucosa of IL-17A KO mice compared with the WT mice. BmEos showed a significantly increased chemotactic response to -low concentration of CCL7 in the presence of IL-17A compared with its absence.
The suppression of nasal inflammation due of IL-17A deficiency in allergic rhinitis is partly responsible for the regulation of CCL7 secretion and eosinophil infiltration, which may be regulated via the CCL7/CCR3 pathway.
在卵清蛋白诱导的变应性鼻炎小鼠模型中，促炎细胞因子白细胞介素（IL）-17A与嗜酸性粒细胞浸润鼻黏膜有关。嗜酸性粒细胞的趋化作用主要通过C-C趋化因子受体3型（CCR3）介导。然而，IL-17A通过趋化因子/趋化因子介导嗜酸性粒细胞募集增强的潜在机制仍不清楚。
在本研究中，我们评估了IL-17A在实验性变应性鼻炎中通过CCL7/CCR3途径对嗜酸性粒细胞相关炎症的作用。
对IL-17A基因敲除（KO）和野生型（WT）BALB/c小鼠进行腹腔注射，并经鼻给予卵清蛋白以诱导变应性鼻炎。评估变应性反应的各种参数，并比较两组鼻组织和血清中CCL7和CCR3的mRNA和蛋白水平。检测来自BALB/c小鼠的骨髓源性嗜酸性粒细胞（bmEos）对有或无IL-17A时CCL7的趋化反应。
在变应性鼻炎模型中，IL-17A缺乏显著减轻了鼻症状、血清IgE水平以及嗜酸性粒细胞向鼻黏膜的募集。与WT小鼠相比，IL-17A KO小鼠鼻黏膜中CCL7和CCR3的mRNA和蛋白水平降低。与不存在IL-17A时相比，bmEos在存在IL-17A时对低浓度CCL7的趋化反应显著增加。
变应性鼻炎中IL-17A缺乏导致的鼻炎症抑制部分归因于CCL7分泌和嗜酸性粒细胞浸润的调节，这可能通过CCL7/CCR3途径进行调控。
