Immunoadjuvant chaperone, GRP170, induces 'danger signals' upon interaction with dendritic cells
Immunoadjuvant chaperone, GRP170, induces 'danger signals' upon interaction with dendritic cells
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DOI：
10.1111/j.1440-1711.2006.01418.x
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发表时间：
2006-04-01
影响因子：
4
通讯作者：
Subjeck, JR
中科院分区：
文献类型：
--
作者：
Manjili, MH;Park, JE;Subjeck, JR
当陪伴肿瘤抗原时，葡萄糖调节蛋白 170 (GRP170) 能够诱导有效的抗肿瘤免疫反应。在本研究中，我们确定了 GRP170 的这种免疫佐剂特性是否也涉及通过与 APC 相互作用诱导“危险信号”的能力。我们在杆状病毒表达系统中制备了重组GRP170，内毒素浓度较低，LPS对树突状细胞（DC）没有任何影响。我们发现GRP170以受体介导的方式结合DC并诱导DC上调MHC II类、CD86和CD40分子的表达，并分泌促炎细胞因子。 GRP170 还在 B16F10 细胞系中诱导 CD40 分子的表达，而 LPS 则不能这样做。这些发现表明，GRP170 通过与 DC 相互作用而充当危险信号，无论其内毒素成分如何。
When chaperoning tumour antigens, glucose-regulated protein 170 (GRP170) is capable of inducing effective antitumour immune responses. In the present study, we determined whether such immunoadjuvant properties of GRP170 also involve the ability to induce 'danger signals' through interaction with APC. We prepared recombinant GRP170 in the baculovirus expression system with low endotoxin concentration at which LPS did not have any effect on dendritic cells (DC). We showed that GRP170 binds DC in a receptor-mediated fashion and induces DC to upregulate the expression of MHC class II, CD86 and CD40 molecules, and to secrete pro-inflammatory cytokines. GRP170 also induced expression of CD40 molecules in a B16F10 cell line, whereas LPS failed to do so. These findings show that GRP170 acts as a danger signal through its interaction with DC, regardless of its endotoxin component.