Kang H S, Lee B S, Yang Y, Park C W, Ha H J, Pyun K H, Choi I
Molecular Biomedicine Research Group, Korea Research Institute of Bioscience and Biotechnology, KIST, Taejon, Republic of Korea.
Cell Immunol. 1996 Mar 15;168(2):174-83. doi: 10.1006/cimm.1996.0064.
Deregulation of IL-6 production is one of the major causes for human multiple myeloma. Exogenous IL-6 stimulated the proliferation of fresh human myeloma cells and the myeloma cell line, U266, which produced IL-6 spontaneously. Anti-IL-6 antibody and IL-6 antisense oligonucleotide suppressed the IL-6 stimulated myeloma cell proliferation, indicating that IL-6 induced the myeloma cell proliferation via an autocrine loop. Okadaic acid, an inhibitor of protein phosphatase 1 and 2A, inhibited the U266 cell proliferation at a concentration of less than 1 ng/ml. At this concentration, okadaic acid suppressed the IL-6-induced IL-6 gene expression of myeloma cells. It seems that the okadaic acid blocked the myeloma cell proliferation by reducing IL-6 synthesis in myeloma cells. In addition, IL-6 itself also regulated IL-6 receptor expression. Analysis by FACScan and RT-PCR showed that anti-IL-6 antibody treatment up-regulated IL-6 receptor expression. Interestingly, the presence of okadaic acid induced the up-regulation of IL-6 receptor expression as well as the down-regulation of IL-6-induced gp130 phosphorylation in the myeloma cells. Taken together, these data suggest that protein phosphatase 1 and 2A are involved in IL-6-mediated autocrine growth of human myeloma cells by modulating IL-6 signaling and IL-6 receptor expression in myeloma cells.
白细胞介素-6（IL-6）产生的失调是人类多发性骨髓瘤的主要病因之一。外源性IL-6刺激新鲜人骨髓瘤细胞和骨髓瘤细胞系U266的增殖，U266可自发产生IL-6。抗IL-6抗体和IL-6反义寡核苷酸抑制IL-6刺激的骨髓瘤细胞增殖，表明IL-6通过自分泌环诱导骨髓瘤细胞增殖。冈田酸是蛋白磷酸酶1和2A的抑制剂，在浓度低于1 ng/ml时可抑制U266细胞增殖。在此浓度下，冈田酸抑制骨髓瘤细胞IL-6诱导的IL-6基因表达。似乎冈田酸通过减少骨髓瘤细胞中IL-6的合成来阻断骨髓瘤细胞增殖。此外，IL-6自身也调节IL-6受体的表达。FACScan分析和逆转录-聚合酶链反应（RT-PCR）显示，抗IL-6抗体处理上调IL-6受体表达。有趣的是，冈田酸的存在也诱导骨髓瘤细胞中IL-6受体表达上调以及IL-6诱导的gp130磷酸化下调。综上所述，这些数据表明蛋白磷酸酶1和2A通过调节骨髓瘤细胞中的IL-6信号传导和IL-6受体表达参与IL-6介导的人骨髓瘤细胞自分泌生长。
