Hanai Yoshiteru, Tokuda Haruhiko, Ohta Toshiki, Matsushima-Nishiwaki Rie, Takai Shinji, Kozawa Osamu
Department of Clinical Laboratory, National Hospital for Geriatric Medicine, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan.
J Cell Biochem. 2006 Dec 15;99(6):1564-71. doi: 10.1002/jcb.21007.
It has been reported that platelet-derived growth factor (PDGF)-BB stimulates the synthesis of interleukin (IL)-6 in osteoblasts. In the present study, we investigated whether the phosphatidylinositol 3-kinase (PI3K)/Akt is involved in the PDGF-BB-induced IL-6 synthesis in osteoblast-like MC3T3-E1 cells. PDGF-BB markedly induced the phosphorylation of Akt and GSK-3beta. Akt inhibitor, 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate, significantly amplified the synthesis of IL-6 by PDGF-BB. The PDGF-BB-induced GSK-3beta phosphorylation was suppressed by the Akt inhibitor. The IL-6 synthesis stimulated by PDGF-BB was markedly enhanced by LY294002 and wortmannin, inhibitors of PI3K. Wortmannin and LY294002 suppressed the PDGF-BB-induced phosphorylation of Akt and GSK-3beta. Taken together, these results strongly suggest that PI3K/Akt negatively regulates the PDGF-BB-stimulated IL-6 synthesis in osteoblasts.
据报道，血小板衍生生长因子（PDGF）-BB可刺激成骨细胞中白细胞介素（IL）-6的合成。在本研究中，我们调查了磷脂酰肌醇3激酶（PI3K）/Akt是否参与PDGF-BB诱导的成骨样MC3T3-E1细胞中IL-6的合成。PDGF-BB显著诱导Akt和糖原合成酶激酶（GSK）-3β的磷酸化。Akt抑制剂1L-6-羟甲基-手性-肌醇2-（R）-2-O-甲基-3-O-十八烷基碳酸酯显著增强了PDGF-BB诱导的IL-6合成。Akt抑制剂可抑制PDGF-BB诱导的GSK-3β磷酸化。PI3K抑制剂LY294002和渥曼青霉素可显著增强PDGF-BB刺激的IL-6合成。渥曼青霉素和LY294002可抑制PDGF-BB诱导的Akt和GSK-3β磷酸化。综上所述，这些结果强烈表明PI3K/Akt负向调节成骨细胞中PDGF-BB刺激的IL-6合成。
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