Abstract：
Secretion of translationally controlled tumor protein (TCTP) was found in body fluids during the late phase of allergic reactions, implicating TCTP in allergic diseases. Furthermore, blocking TCTP has been shown to be helpful in treating asthma and allergies in animal models. The objectives of this study were to produce anti-TCTP monoclonal antibodies (mAbs), test their ability to inhibit the cytokine-like function of dimeric TCTP (dTCTP) in vitro and to assess their therapeutic effects in a murine model of ovalbumin (OVA)-induced airway inflammation. We first verified the inhibitory effects of 4 anti-TCTP mAbs on dTCTP-induced secretion of IL-8 in BEAS-2B cells. To investigate the anti-inflammatory effect of anti-TCTP mAbs on allergic airway inflammation, we treated OVA-sensitized mice with anti-TCTP mAbs before OVA challenge. The changes in bronchoalveolar lavage fluid (BALF) cells, IL-4, IL-5, and IL-13 levels in both BALF and lung homogenates, plasma levels of OVA-specific IgE, and lung tissues were analyzed. We found that JEW-M449 anti-TCTP mAb bound to the flexible loop of TCTP and significantly inhibited dTCTP-induced IL-8 release, making it the most effective inhibitor in our study. We also found that treatment with JEW-M449 significantly reduced the infiltration of inflammatory cells and suppressed the OVA-induced upregulation of type 2 cytokines in both BALF and lung homogenates in a dose-dependent manner. In addition, JEW-M449 significantly attenuated the degree of goblet cell hyperplasia and mucus secretion. Our results demonstrate that specific targeting of the flexible loop of TCTP is a potent strategy for treating airway inflammatory diseases.
摘要：
在过敏反应的后期，体液中发现了翻译控制的肿瘤蛋白（TCTP）的分泌，TCTP与过敏性疾病有关。此外，在动物模型中,阻断TCTP已被证明有助于治疗哮喘和过敏.本研究的目的是产生抗TCTP单克隆抗体（mAb），测试它们在体外抑制二聚体TCTP（dTCTP）的细胞因子样功能的能力，并评估它们在卵清蛋白（OVA）诱导的气道炎症的小鼠模型中的治疗效果。我们首先验证了4种抗TCTPmAb对dTCTP诱导的BEAS-2B细胞分泌IL-8的抑制作用。探讨抗TCTP单克隆抗体对过敏性气道炎症的抗炎作用,我们在OVA攻击前用抗TCTPmAb治疗OVA致敏小鼠。支气管肺泡灌洗液（BALF）细胞的变化，BALF和肺匀浆中IL-4、IL-5和IL-13水平,OVA特异性IgE的血浆水平，并对肺组织进行分析。我们发现JEW-M449抗TCTPmAb与TCTP的柔性环结合，并显着抑制dTCTP诱导的IL-8释放，使其成为我们研究中最有效的抑制剂。我们还发现，用JEW-M449治疗可显着减少炎症细胞的浸润，并以剂量依赖性方式抑制OVA诱导的BALF和肺匀浆中2型细胞因子的上调。此外,JEW-M449可显着减弱杯状细胞增生和粘液分泌的程度。我们的结果表明，TCTP柔性环的特异性靶向是治疗气道炎症性疾病的有效策略。
