Notch ligand Delta-like4 inhibits the development of murine experimental allergic conjunctivitis
Notch ligand Delta-like4 inhibits the development of murine experimental allergic conjunctivitis
复制标题
DOI：
10.1016/j.imlet.2008.10.006
复制
发表时间：
2008-12-22
影响因子：
4.4
通讯作者：
Yagita, Hideo
中科院分区：
文献类型：
--
作者：
Fukushima, Atsuki;Sumi, Tamaki;Yagita, Hideo
背景资料：探讨Notch配体在小鼠实验性过敏性结膜炎（EC）发生中的作用。方法：为了诱导EC，用明矾中的豚草（RW）免疫野生型（WT）或IFIN-γ缺陷（GKO）Balb/c小鼠，然后用滴眼液中的RW攻击。RW攻击后24小时，收获结膜、脾脏和血液以分别评价结膜嗜酸性粒细胞浸润、RW特异性细胞因子产生和血清IG水平。在诱导期或效应期，将抗Notch配体的Ab（抗锯齿蛋白1、抗锯齿蛋白2、抗Delta样（Dll）1和抗Dll 4）腹膜内注射到EC发育小鼠中。作为对照，注射正常仓鼠IgG（nhIgG）。结果如下：在诱导期用抗Dll 4 Ab而不是其它Ab治疗显著增加EC的严重程度，如通过结膜嗜酸性粒细胞浸润所测量的。抗-Dll 4 Ab治疗也显著上调RW-回忆IL-4产生并抑制血清IgE和IgG 1水平。然而，在诱导阶段期间的抗Dll 4 Ab治疗并不显著影响GKO小鼠中EC的严重程度。没有显着影响EC，脾细胞细胞因子的产生，或血清IG水平的严重程度时，在效应phase.Conclusions：这些观察结果表明，Dll 4，一个Notch配体，在抑制EC的发展中发挥作用，可能是通过提供一个负信号的Th 2发展在诱导阶段。此外，IFN-γ可能参与抗Dll 4 Ab治疗对EC的增强作用。(C)2008年由Elsevier B. V.出版。
Background: To investigate the involvement of Notch ligands in the development of experimental allergic conjunctivitis (EC) in mice.Methods: To induce EC, wild-type (WT) or IFIN-gamma-deficient (GKO) BALB/c mice were immunized with ragweed (RW) in alum followed by RW challenge in eye drops. Twenty-four hours after RW challenge, the conjunctivas, spleens and blood were harvested to evaluate conjunctival eosinophil infiltration, RW-specific cytokine production and serum Ig levels, respectively. Abs against Notch ligands (anti-Jagged1, anti-Jagged2, anti-Delta-like (Dll)1 and anti-Dll4) were injected intraperitoneally into EC-developing mice during the induction or effector phase. As a control, normal hamster IgG (nhIgG) was injected. Results: Treatment with anti-Dll4 Ab but not the other Abs during the induction phase significantly augmented the severity of EC, as measured by the conjunctival eosinophil infiltration. Anti-Dll4 Ab treatment also significantly upregulated RW-recall IL-4 production and suppressed serum IgE and IgG1 levels. However, anti-Dll4 Ab treatment during the induction phase did not significantly affect the severity of EC in GKO mice. None of the Abs significantly affected the severity of EC, splenocyte cytokine production, or serum Ig levels when administered during the effector phase.Conclusions: These observations suggest that Dll4, a Notch ligand, plays a role in suppressing the development of EC, possibly by providing a negative signal for Th2 development during the induction phase. In addition, IFN-gamma may participate in the augmentation of EC by anti-Dll4 Ab treatment. (C) 2008 Published by Elsevier B.V.