Interleukin-8 stimulation of osteoclastogenesis and bone resorption is a mechanism for the increased osteolysis of metastatic bone disease
Interleukin-8 stimulation of osteoclastogenesis and bone resorption is a mechanism for the increased osteolysis of metastatic bone disease
复制标题
DOI：
10.1016/s8756-3282(03)00086-3
复制
发表时间：
2003-07-01
期刊：
影响因子：
4.1
通讯作者：
Suva, LJ
中科院分区：
文献类型：
--
作者：
Bendre, MS;Montague, DC;Suva, LJ
白细胞介素 8 (IL-8) 是细胞因子 α 趋化因子家族的成员，最初被鉴定为中性粒细胞趋化剂。最近，我们报道说，IL-8 水平升高与人类乳腺癌细胞群骨转移增加相关，但与甲状旁腺激素相关蛋白 (PTHrP) 水平无关。我们假设乳腺癌细胞的 IL-8 表达会通过附近的基质细胞间接影响破骨细胞生成或直接影响破骨细胞分化和活性。在本研究中，我们研究了 IL-8 在破骨细胞形成和骨吸收过程中的作用，这与转移性乳腺癌相关。向基质成骨细胞培养物中添加重组人 (rh) IL-8 (10 ng/ml) 可刺激 RANKL mRNA 表达和蛋白质产生，但对骨保护素的表达没有影响。此外，rhIL-8还直接刺激人外周血单个核细胞分化为骨吸收破骨细胞。在这些培养物中，即使存在过量 (200 ng/ml) RANK-Fc，IL-8 也能够刺激人破骨细胞形成。 IL-8 对破骨细胞及其祖细胞的影响与细胞表面 IL-8 特异性受体 (CXCR1) 的表达有关。这些结果证明IL-8对破骨细胞分化和活性有直接影响。总之，这些数据表明 IL-8 与转移性乳腺癌相关的骨溶解有关。 (C) 2003 年爱思唯尔科学（美国）。版权所有。
Interleukin 8 (IL-8) is a member of the alpha chemokine family of cytokines originally identified as a neutrophil chemoattractant. Recently, we reported that elevated levels of IL-8, but not parathyroid hormone-related protein (PTHrP), correlated with increased bone metastasis in a population of human breast cancer cells. We hypothesized that IL-8 expression by breast cancer cells would either indirectly influence osteoclastogenesis via nearby stromal cells or directly influence osteoclast differentiation and activity. In the present study, we investigated the role of IL-8 in the process of osteoclast formation and bone resorption, which is associated with metastatic breast cancer. The addition of recombinant human (rh) IL-8 (10 ng/ml) to cultures of stromal osteoblastic cells stimulated both RANKL mRNA expression and protein production, with no effect on the expression of osteoprotegerin. In addition, rhIL-8 also directly stimulated the differentiation of human peripheral blood mononuclear cells into bone-resorbing osteoclasts. In these cultures, IL-8 was able to stimulate human osteoclast formation even in the presence of excess (200 ng/ml) RANK-Fc. The effect of IL-8 on osteoclasts and their progenitors was associated with the cell surface expression of the IL-8-specific receptor (CXCR1) on the cells. These results demonstrate a direct effect of IL-8 on osteoclast differentiation and activity. Together, these data implicate IL-8 in the osteolysis associated with metastatic breast cancer. (C) 2003 Elsevier Science (USA). All rights reserved.