Dehydroepiandrosterone can inhibit the proliferation of myeloma cells and the interleukin-6 production of bone marrow mononuclear cells from patients with myeloma
Dehydroepiandrosterone can inhibit the proliferation of myeloma cells and the interleukin-6 production of bone marrow mononuclear cells from patients with myeloma
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DOI：
10.1158/0008-5472.can-04-3079
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发表时间：
2005-03-15
期刊：
影响因子：
11.2
通讯作者：
Kawano, MM
中科院分区：
文献类型：
--
作者：
Liu, SQ;Ishikawa, H;Kawano, MM
血清中的肾上腺性激素，硫酸脱氢表雄酮（DHEA-S），显着降低人骨髓瘤相比，随着年龄的生理下降带来的减少。为了阐明DHEA对骨髓瘤细胞的作用，我们研究了DHEA和DHEA-S是否能抑制骨髓瘤患者骨髓单个核细胞产生白细胞介素-6（IL-6）和骨髓瘤细胞增殖。DHEA-S和DHEA抑制骨髓基质细胞系KM-102以及骨髓瘤患者骨髓单核细胞产生IL-6。此外，DHEA抑制U-266细胞系和患者的原代骨髓瘤细胞的体外生长，以及严重联合免疫缺陷-hIL 6转基因小鼠中腹膜内植入的U-266细胞的体内生长。DHEA可上调骨髓瘤细胞和骨髓基质细胞中过氧化物酶体增殖物激活受体（PPAR）、PPAR β的表达，但不上调PPAR γ和PPAR α的表达以及I κ B α基因的表达，这可能是DHEA通过下调NF-κ B活性而抑制IL-6产生的原因。因此，这些数据显示DHEA-S以及DHEA对骨髓瘤和骨髓基质细胞具有直接作用，分别抑制其增殖和IL-6产生。
The serum levels of an adrenal sex hormone, dehydroepiandrosterone sulfate (DHEA-S), are significantly more decreased in human myelomas compared with the reduction brought by physiologic decline with age. In order to clarify the effect of DHEA on myeloma cells, we investigated whether DHEA and DHEA-S could inhibit interleukin-6 (IL6) production of bone marrow mononuclear cells and the proliferation of myeloma cells from patients with myeloma. DHEA-S and DHEA suppressed IL-6 production from a bone marrow stromal cell line, KM-102, as well as in bone marrow mononuclear cells from patients with myeloma. Furthermore, DHEA inhibited in vitro growth of the U-266 cell line and primary myeloma cells from the patients, as well as the in vivo growth of U-266 cells implanted i.p. in severe combined immunodeficiency-hIL6 transgenic mice. DHEA up-regulated the expression of peroxisome proliferator-activated receptor (PPAR), PPAR beta, but not PPAR gamma or PPAR alpha, and the expression of I kappa B alpha gene in myeloma cells and bone marrow stromal cells, which could explain the suppressive effect of DHEA on IL-6 production through the down-regulation of NF-kappa B activity. Therefore, these data revealed that DHEA-S, as well as DHEA, had a direct effect on myeloma and bone marrow stromal cells to inhibit their proliferation and IL-6 production, respectively.