Center for Human Disease Genomics, Peking University, 38 Xueyuan Road, Beijing 100191, PR China.
Int Immunopharmacol. 2011 Dec;11(12):2188-93. doi: 10.1016/j.intimp.2011.09.017. Epub 2011 Oct 12.
Human chemokine-like factor (CKLF1) is a human cytokine that exhibits chemotactic activities on a wide spectrum of leukocytes. One of CKLF1's C-terminal peptides, C19, exerts inhibitory effects on chemotaxis mediated by mouse Ccr3 and Ccr4 and human CCR3 and CCR4. Mouse models of asthma show that C19 can also inhibit the Th2 response. CCR3 and CCR4 are chemokine receptors important to allergic rhinitis, a condition whose pathogenesis is similar to that of asthma. Here, we established a mouse model of allergic rhinitis by repetitive sensitization and intranasal challenge with OVA and assessed whether C19 has therapeutic effects on this model. In this study, both intranasal and intraperitoneal administration of C19 reduced allergic symptoms such as sneezing and rubbing and serum concentration of IgE. C19 showed a strong ability to suppress eosinophil accumulation in nasal mucosa and lung tissues. C19 was able to suppress the Th2 cytokine IL-4 without augmenting the Th1 cytokine IFN-γ in BAL and IL-4(+) cells in the local nasal tissue. In terms of symptom amelioration, IgE reduction, and eosinophilia suppression, C19 was found to be as effective against allergic rhinitis as Budesonide. Moreover, intranasal treatment has a stronger therapeutic effect than other types of administration, and it may be more convenient and safe. For these reasons, C19 may have potential in the treatment of allergic rhinitis.
人源趋化因子样因子 1(CKLF1)是一种细胞因子,对多种白细胞具有趋化活性。CKLF1 的 C 末端肽之一 C19 对小鼠 Ccr3 和 Ccr4 以及人 CCR3 和 CCR4 介导的趋化作用具有抑制作用。哮喘的小鼠模型表明,C19 还可以抑制 Th2 反应。CCR3 和 CCR4 是过敏性鼻炎的重要趋化因子受体,其发病机制与哮喘相似。在这里,我们通过重复致敏和鼻内 OVA 挑战建立了过敏性鼻炎的小鼠模型,并评估了 C19 对该模型是否具有治疗作用。在这项研究中,C19 的鼻内和腹腔内给药均减轻了打喷嚏和摩擦等过敏症状,以及血清 IgE 浓度。C19 显示出强烈抑制鼻黏膜和肺组织嗜酸性粒细胞积累的能力。C19 能够抑制 Th2 细胞因子 IL-4,而不增强 BAL 中的 Th1 细胞因子 IFN-γ 和局部鼻组织中的 IL-4(+)细胞。在症状改善、IgE 减少和嗜酸性粒细胞减少方面,C19 对过敏性鼻炎的疗效与布地奈德相当。此外,鼻内治疗比其他类型的给药具有更强的治疗效果,并且可能更方便和安全。因此,C19 可能在过敏性鼻炎的治疗中有一定的潜力。