Prostaglandin D2induces interleukin-6 synthesis via Ca2+mobilization in osteoblasts: regulation by protein kinase C
Prostaglandin D2induces interleukin-6 synthesis via Ca2+mobilization in osteoblasts: regulation by protein kinase C
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前列腺素 D2 通过成骨细胞中的 Ca2 动员诱导白细胞介素 6 合成：蛋白激酶 C 的调节
DOI：
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
T. Uematsu
中科院分区：
文献类型：
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作者：
H. Tokuda;O. Kozawa;A. Harada;T. Uematsu
我们先前表明，前列腺素（PG）D2刺激Ca 2+从细胞外空间流入，并激活磷酸肌醇（PI）水解磷脂酶C和磷脂酰胆碱（PC）水解磷脂酶D独立于PGE 2或PGF 2 α成骨样MC 3 T3-E1细胞。本研究探讨了PGD 2对MC 3 T3-E1细胞合成白细胞介素-6（IL-6）的影响及其调控机制。在10 nM和10 μ M之间的范围内，PGD 2剂量依赖性地显著刺激IL-6合成。EGTA对细胞外Ca ~（2+）的耗竭可降低PGD_2诱导的IL-6合成。细胞内Ca ~（2+）动员抑制剂TMB-8可显著抑制PGD_2诱导的IL-6合成。另一方面，蛋白激酶C（PKC）的特异性抑制剂calphostin C可增强PGD 2诱导的IL-6的合成。此外，U-73122，磷脂酶C的抑制剂，和普萘洛尔，磷脂酸磷酸水解酶抑制剂，增强PGD 2诱导的IL-6的合成。这些结果有力地表明，PGD 2刺激IL-6的合成，通过细胞内Ca 2+动员成骨细胞，并通过PGD 2本身的PKC激活调节IL-6的过度合成。
We previously showed that prostaglandin (PG) D2 stimulates Ca2+ influx from extracellular space and activates phosphoinositidic (PI)-hydrolyzing phospholipase C and phosphatidylcholine (PC)-hydrolyzing phospholipase D independently from PGE2 or PGF2alpha in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the effect of PGD2 on the synthesis of interleukin-6 (IL-6) and its regulatory mechanism in MC3T3-E1 cells. PGD2 significantly stimulated IL-6 synthesis dose-dependently in the range between 10 nM and 10 microM. The depletion of extracellular Ca2+ by EGTA reduced the PGD2-induced IL-6 synthesis. TMB-8, an inhibitor of intracellular Ca2+ mobilization, significantly inhibited the PGD2-induced IL-6 synthesis. On the other hand, calphostin C, a specific inhibitor of protein kinase C (PKC), enhanced the synthesis of IL-6 induced by PGD2. In addition, U-73122, an inhibitor of phospholipase C, and propranolol, a phosphatidic acid phosphohydrolase inhibitor, enhanced the PGD2-induced IL-6 synthesis. These results strongly suggest that PGD2 stimulates IL-6 synthesis through intracellular Ca2+ mobilization in osteoblasts, and that the PKC activation by PGD2 itself regulates the over-synthesis of IL-6.
血小板衍生生长因子刺激成骨细胞谱系细胞中白细胞介素 6 的合成。
DOI：
10.1210/endo.136.12.7588297
发表时间：
1995
期刊：
Endocrinology.
影响因子：
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作者：
Franchimont,N;Canalis,E
通讯作者：
Canalis,E
前列腺素调节成骨细胞功能。
DOI：
10.1152/ajprenal.1989.257.5.f755
发表时间：
1989
期刊：
The American journal of physiology
影响因子：
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作者：
Yamaguchi,DT;Green,J;Merritt,BS;Kleeman,CR;Muallem,S
通讯作者：
Muallem,S