Antitumor and immunomodulatory effects of recombinant fusion protein rMBP-NAP through TLR-2 dependent mechanism in tumor bearing mice
Antitumor and immunomodulatory effects of recombinant fusion protein rMBP-NAP through TLR-2 dependent mechanism in tumor bearing mice
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重组融合蛋白rMBP-NAP通过TLR-2依赖性机制对荷瘤小鼠的抗肿瘤和免疫调节作用
DOI：
10.1016/j.intimp.2015.08.027
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发表时间：
2015
影响因子：
5.6
通讯作者：
Kang Qiaozhen
中科院分区：
文献类型：
--
作者：
Wang Ting;Liu Xilong;Ji Zhenyu;Men Yingli;Du Mingxuan;Ding Cong;Wu Yahong;Liu Xin;Kang Qiaozhen
幽门螺杆菌中性粒细胞激活蛋白(HP-NAP)的促炎和免疫调节特性不仅使其在疾病发病机制中发挥重要作用，而且使其成为潜在的治疗应用，包括疫苗和药物开发。我们前期的工作表明，重组HP-NAP与大肠杆菌麦芽糖结合蛋白(rMBP-NAP)的融合在调节Th1细胞的分化中起着重要作用。在本研究中，我们利用两种小鼠肝癌H22和肉瘤S180模型，研究了rMBP-NAP诱导抗肿瘤免疫的能力。小鼠皮下注射rMBP-NAP后，肿瘤生长较对照小鼠减少约40%-50%。经rMBP-NAP治疗的荷瘤小鼠的脾细胞显示出明显的CD_4+干扰素-γ分泌细胞，这是Th1细胞的一种细胞因子谱。此外，静脉注射TLR2封闭抗体T2.5可显著降低rMBP-NAP的抗肿瘤作用和rMBP-NAP诱导的干扰素-γ的产生。我们的发现表明，rMBP-NAP有可能成为开发免疫调节性抗肿瘤药物的候选药物。
The pro-inflammatory and immunomodulatory properties of Helicobacter pylori neutrophil activating protein (Hp-NAP) not only make it to play an important role in disease pathogenesis but also make it to be a potential candidate for therapeutic applications, including vaccine and drug development. Our previous work demonstrated that the recombinant Hp-NAP fused with the maltose binding protein ofEscherichia coli(rMBP-NAP) play an important role in regulating the differentiation of Th1 cells. In this study, we investigated the ability of rMBP-NAP to induce antitumor immunity using two murine models of hepatoma H22 and sarcoma S180. Subcutaneous administration of mice with rMBP-NAP resulted in an about 40%–50% decrease of tumor growth compared with that of the control mice. Splenocytes from the tumor-bearing mice treated with rMBP-NAP showed a significant accumulation of CD4+IFN-γ-secreting cells, which is a cytokine profile of Th1 cells. Furthermore, intravenous injection of T2.5, toll like receptor (TLR) 2 blocking antibody, significantly recede the antitumor effect of rMBP-NAP and the production of IFN-γ induced by rMBP-NAP. Our findings indicate that potentiality of rMBP-NAP to be a candidate for the development of immunomodulatory antitumoral drugs.