ATP-stimulated interleukin-6 synthesis through P2Y receptors on human osteoblasts
ATP-stimulated interleukin-6 synthesis through P2Y receptors on human osteoblasts
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DOI：
10.1016/j.bbrc.2004.11.037
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发表时间：
2005-01-14
影响因子：
3.1
通讯作者：
Togari, A
中科院分区：
文献类型：
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作者：
Ihara, H;Hirukawa, K;Togari, A
我们研究了细胞外三磷酸腺苷（ATP）对白细胞介素（IL）-6产生的影响。其分子能够刺激破骨细胞从其造血前体发育成破骨细胞，并参与人成骨细胞SaM-1细胞中的信号转导系统。这些人成骨细胞组成性表达P2 X4、P2 X5、P2 X6、P2 Y2、P2 Y 5和P2 Y 6嘌呤能受体。ATP增加SaM-1细胞IL-6基因和蛋白的表达。IL-6 mRNA的表达在1 h达到最大，并且响应于ATP（10-100 M）的IL-6合成的增加以浓度依赖性方式发生。在对IL-6合成有效的核苷酸的相同浓度范围内，ATP引起细胞内Ca 2+浓度（[Ca 2 +]（i））的增加，这种增加被苏拉明（一种P2 Y受体拮抗剂）或2-氨基乙氧基二苯基硼酸酯（2-APB）（一种肌醇1，4，5-三磷酸受体阻断剂）预处理抑制，但不被细胞外Ca 2+螯合剂EGTA抑制。用苏拉明或2-APB预处理SaM-1细胞也可抑制ATP引起的IL-6合成增加。这些研究结果表明，细胞外ATP诱导的IL-6的合成发生通过P2 Y受体和动员钙从内部存储在人成骨细胞。(C)2004年爱思唯尔公司All rights reserved.
We investigated the effect of extracellular adenosine triphosphate (ATP) on the production of interleukin (IL)-6. whose molecules are capable of stimulating the development of osteoclasts from their hematopoietic precursors as well as are involved in signal transduction systems in human osteoblastic SaM-1 cells. These human osteoblasts Constitutively expressed P2X4, P2X5, P2X6, P2Y2, P2Y5, and P2Y6 purinergic receptors. ATP increased gene- and protein-expression of IL-6 in SaM-1 cells. The expression of the IL-6 mRNA was maximal at I h, and the increase in IL-6 synthesis in response to ATP (10-100 M) occurred in a concentration-dependent manner. Over the same concentration range of the nucleotide that was effective for IL-6 synthesis, ATP caused an increase in the intracellular Ca2+ concentration ([Ca2+](i)), which increase was inhibited by pretreatment with suramin, a P2Y receptor antagonist, or 2-aminoethoxydiphenyl borate (2-APB), an inositol 1,4,5-trisphosphate receptor blocker, but not by the extracellular Ca2+-chelating agent EGTA. The pretreatment of SaM-1 cells with suramin or 2-APB also inhibited the increase in IL-6 synthesis in response to ATP. These findings suggest that extracellular ATP-induced IL-6 synthesis occurs through P2Y receptors and mobilization of Ca2+ from internal stores in human osteoblastic cells. (C) 2004 Elsevier Inc. All rights reserved.