Triggering of toll-like receptor-4 in human multiple myeloma cells promotes proliferation and alters cell responses to immune and chemotherapy drug attack
Triggering of toll-like receptor-4 in human multiple myeloma cells promotes proliferation and alters cell responses to immune and chemotherapy drug attack
复制标题
触发人多发性骨髓瘤细胞中的 Toll 样受体 4 可促进增殖并改变细胞对免疫和化疗药物攻击的反应
DOI：
10.4161/cbt.11.1.13878
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发表时间：
2011-01-01
影响因子：
3.6
通讯作者：
Cai, Zhen
中科院分区：
文献类型：
--
作者：
Bao, Hanying;Lu, Peilin;Cai, Zhen
多发性骨髓瘤(MM)是一种无法治愈的B细胞恶性肿瘤，其特征是恶性浆细胞在骨髓中积聚，并伴有反复或持续的感染。Toll样受体(Toll-like Receptor，TLRs)在宿主抵抗感染中起着至关重要的作用。本研究的目的是研究TLR在MM细胞中启动的反应，包括增殖、抗凋亡和免疫逃逸。采用逆转录聚合酶链式反应、实时荧光定量聚合酶链式反应、免疫印迹、酶联免疫吸附试验和流式细胞仪检测骨髓瘤细胞系的基因转录、细胞周期和蛋白表达。H-3-胸腺嘧啶核苷检测细胞增殖，Annexin V-PI流式细胞仪检测细胞凋亡。我们发现，表达TLRs和脂多糖的人骨髓瘤细胞株诱导了细胞增殖，并部分保护了MM.1S和ARP-1细胞免受阿霉素诱导的凋亡。脂多糖可能通过MyD88和MAPKs信号途径诱导细胞增殖。此外，脂多糖还可上调骨髓瘤细胞分泌细胞因子IL-18和免疫调节因子B7-H1、B7-H2和CD40的mRNA表达，帮助骨髓瘤细胞逃避免疫监视。我们的结果表明，TLRs对骨髓瘤细胞具有功能性，这些TLRs的配体在影响骨髓瘤细胞的增殖、生存以及对化疗和免疫攻击的应答方面具有功能作用。
Multiple myeloma (MM) is an incurable B-cell malignancy characterized by accumulation of malignant plasma cells in the bone marrow and by recurrent or persistent infections. Toll-like receptors (TLRs) are essential in the host defense against infections. The aim of this study was to investigate TLR initiated responses in MM cells including proliferation, antiapoptosis and immune escape. Myeloma cell lines gene transcription, cell cycle and protein expression were detected by RT-PCR, real-time PCR, western blot, ELISA and flow cytometry analysis. H-3-thymidine was used for measuring cell proliferation and Annexin V-PI flow cytometry for the detection of cell apoptosis. We show that human myeloma cell lines expressed TLRs and LPS induced the proliferation and partially protected MM.1S and ARP-1 cells from adriamycin-induced apoptosis. LPS appears to induce proliferation via MyD88 and MAPKs signaling. In addition, LPS treatment upregulated myeloma cell secretion of cytokine IL-18 and expression of immunoregulatory factors B7-H1, B7-H2 and CD40 mRNA and helped myeloma cells to escape immune surveillance. Our results show that TLRs are functional on myeloma tumor cells and the ligands to these TLRs have a functional role in affecting myeloma cell proliferation, survival and response to chemotherapy and immune attacks.