Interleukin 6 induces monocyte chemoattractant protein-1 expression in myeloma cells
Interleukin 6 induces monocyte chemoattractant protein-1 expression in myeloma cells
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DOI：
10.1038/sj.leu.2402714
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发表时间：
2002-10-01
期刊：
影响因子：
11.4
通讯作者：
Jelinek, DF
中科院分区：
文献类型：
--
作者：
Arendt, BK;Velazquez-Dones, A;Jelinek, DF
白介素6(IL-6)在多发性骨髓瘤恶性浆细胞的生物学过程中起重要作用。为了更好地了解IL-6刺激骨髓瘤细胞的生长，我们进行了基因表达谱分析，以确定IL-6的早期反应基因。在KAS-6/1IL-6依赖的人骨髓瘤细胞系中，IL-6刺激可显著诱导单核细胞趋化蛋白-1(MCP-1)mRNA的表达。为了验证这一结果，我们使用了逆转录聚合酶链式反应和核糖核酸酶保护试验，并用这两种试验证明了MCP-1在各种IL-6反应性骨髓瘤细胞系中确实是一个IL-6反应性基因。此外，我们还证明了IL-6刺激骨髓瘤细胞系和新鲜患者肿瘤细胞分泌MCP-1。最后，我们提出的证据表明，新鲜的患者肿瘤细胞表达MCP-1受体CCR2的mRNA，骨髓瘤细胞株以及第二个MCP-1受体CCR11也是如此。虽然MM细胞对MCP-1的趋化作用很小，但我们能够证明MCP-1能刺激MAPK的激活。由于这种趋化因子在血管生成和骨稳态中发挥重要作用，以及MCP-1激活骨髓瘤细胞的能力，这些结果提示了IL-6可能参与疾病发病的新机制。
Interleukin 6 (IL-6) is known to play an important role in the biology of the malignant plasma cells in multiple myeloma. In an effort to better understand IL-6 stimulated myeloma cell growth, we have performed gene expression profiling to identify IL-6 early response genes. Using the KAS-6/1 IL-6-dependent human myeloma cell line, IL-6 stimulation dramatically induced expression of monocyte chemoattractant protein-1 (MCP-1) mRNA. To verify this result, we used reverse transcriptase PCR and RNAse protection assays and demonstrated using both assays that MCP-1 is indeed an IL-6 responsive gene in a variety of IL-6-responsive myeloma cell lines. Moreover, we also demonstrated IL-6 stimulated MCP-1 secretion by the myeloma cell lines as well as by fresh patient tumor cells. Lastly, we present evidence that fresh patient tumor cells express mRNA for the MCP-1 receptor, CCR2, as do myeloma cell lines along with a second MCP-1 receptor, CCR11. Although MM cell chemotaxis in response to MCP-1 was only minimal, we were able to demonstrate that MCP-1 stimulated activation of MAPK. Because of the important role that this chemokine plays in both angiogenesis and bone homeostasis, and the ability of MCP-1 to activate myeloma cells, these results suggest a new mechanism by which IL-6 may contribute to disease pathogenesis.