Interleukin-32α promotes the proliferation of multiple myeloma cells by inducing production of IL-6 in bone marrow stromal cells.
Interleukin-32α promotes the proliferation of multiple myeloma cells by inducing production of IL-6 in bone marrow stromal cells.
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Interleukin-32alpha 通过诱导骨髓基质细胞产生 IL-6 来促进多发性骨髓瘤细胞的增殖。
DOI：
10.18632/oncotarget.21611
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发表时间：
2017-11-03
期刊：
影响因子：
--
通讯作者：
Cai Z
中科院分区：
文献类型：
--
作者：
Lin X;Yang L;Wang G;Zi F;Yan H;Guo X;Chen J;Chen Q;Huang X;Li Y;Zhang E;Wu W;Yang Y;He D;He J;Cai Z
多发性骨髓瘤（MM）是一种与炎症密切相关的恶性浆细胞疾病。在MM骨髓微环境中，骨髓基质细胞（BMSCs）是分泌白细胞介素-6（IL-6）的主要来源，促进MM细胞的增殖和进展。然而，微环境如何刺激BMSC分泌IL-6仍不清楚。白细胞介素-32（IL-32）是一种新近发现的促炎因子。据报道，在实体瘤中，IL-32诱导其他炎症因子（包括IL-6、IL-10和TNF-α）的变化。本研究的目的是研究IL-32在MM骨髓微环境中的表达及其作用。我们的数据说明MM患者在骨髓和外周血中比健康个体具有更高的IL-32表达。我们使用ELISA和qRT-PCR发现恶性浆细胞是MM骨髓中IL-32产生的主要来源。ELISA和Western blot分析表明，重组IL-32α通过激活NF-κB和STAT 3信号通路诱导BMSCs产生IL-6，而IL-32受体PR 3的下调则抑制了这一过程。shRNA敲低IL-32可抑制骨髓间充质干细胞诱导的MM细胞增殖。结论：MM细胞分泌的IL-32具有旁分泌作用，可诱导BMSCs产生IL-6，从而反馈促进MM细胞生长。
Multiple myeloma (MM) is a malignant plasma disease closely associated with inflammation. In MM bone marrow microenvironment, bone marrow stromal cells (BMSCs) are the primary source of interleukin-6 (IL-6) secretion, which promotes the proliferation and progression of MM cells. However, it is still unknown how the microenvironment stimulates BMSCs to secrete IL-6. Interleukin-32 (IL-32) is a newly identified pro-inflammatory factor. It was reported that in solid tumors, IL-32 induces changes in other inflammatory factors including IL-6, IL-10, and TNF-α. The aim of this study was to investigate the expression of IL-32 and the role of IL-32 in the MM bone marrow microenvironment. Our data illustrate that MM patients have higher expression of IL-32 than healthy individuals in both bone marrow and peripheral blood. We used ELISA and qRT-PCR to find that malignant plasma cells are the primary source of IL-32 production in MM bone marrow. ELISA and Western blot analysis revealed that recombinant IL-32α induces production of IL-6 in BMSCs by activating NF-κB and STAT3 signaling pathways, konckdown of IL-32 receptor PR3 inhibit this process. Knockdown of IL-32 by shRNA decreased the proliferation in MM cells that induced by BMSCs. In conclusion, IL-32 secreted from MM cells has paracrine effect to induce production of IL-6 in BMSCs, thus feedback to promote MM cells growth.
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影响因子：
--
作者：
Li Y;Zheng Y;Li T;Wang Q;Qian J;Lu Y;Zhang M;Bi E;Yang M;Reu F;Yi Q;Cai Z
通讯作者：
Cai Z
影响因子：
4.6
作者：
Khawar MB;Abbasi MH;Sheikh N
通讯作者：
Sheikh N
影响因子：
11.4
作者：
Jego, G;Bataille, R;Pellat-Deceunynck, C
通讯作者：
Pellat-Deceunynck, C
影响因子：
4.4
作者：
Bai, Xiyuan;Kim, Soo-Hyun;Chan, Edward D.
通讯作者：
Chan, Edward D.
影响因子：
15.9
作者：
Gao, Sizhi Paul;Mark, Kevin G.;Bromberg, Jacqueline F.
通讯作者：
Bromberg, Jacqueline F.