• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cytokine >The effects of dexamethasone and dehydroepiandrosterone (DHEA) on cytokines and receptor expression in a human osteoblastic cell line: Potential steroid-sparing role for DHEA.
【24h】

The effects of dexamethasone and dehydroepiandrosterone (DHEA) on cytokines and receptor expression in a human osteoblastic cell line: Potential steroid-sparing role for DHEA.

机译：地塞米松和脱氢表雄酮（DHEA）对人成骨细胞系中细胞因子和受体表达的影响：DHEA的潜在类固醇保护作用。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Osteoporosis and associated fractures are the most common and debilitating complication of glucocorticoid use. The use of alternative anti-inflammatory agents without the deleterious skeletal effects of glucocorticoids is needed. Dehydroepiandrosterone (DHEA) may have immunomodulatory as well as positive effects on bone. For our further understanding of the mechanisms of action of DHEA, as a steroid-sparing agent, we investigated and compared the effects of dexamethasone (DEX) and DHEA on the regulation of the downstream effector pathway of osteoclastogenesis; RANKL/OPG and a range of inflammatory/pro-resorbing cytokines and receptors using a human clonal osteoblastic cell line. The cells were treated with DEX, DHEA, and androstenedione (ANDI). The mRNA expression of RANKL and OPG was determined by real-time PCR after overnight incubation. The regulation of a broad spectrum of cytokines by DEX and DHEA was also investigated using a human cytokine/growth factor and receptor gene array consisting of 268 cytokine-related cDNAs. To confirm some of the gene expression changes, protein production was measured by ELISA. RANKL expression and RANKL/OPG ratio were increased by DEX. This effect was reversed by co-treatment with both DHEA or ANDI. Several pro-inflammatory/resorptive cytokines including IL-6, IL-4, IFN-gamma, macrophage inhibitory factor (MIF) were down-regulated not only by DEX but also by DHEA. In contrast to DEX, DHEA did not lead to suppression of growth factors including vascular endothelial growth factor (VEGF), fibroblast growth factor-5 (FGF-5), insulin-like growth factor-binding protein3 (IGF-BP3). Several new target genes previously documented to influence bone formation were up-regulated by DHEA such as Notch 2, insulin receptor, thrombin receptor (PAR1). The data suggest that DHEA has immunomodulatory properties without the catabolic effects on bone remodeling, observed with glucocorticoid use. DHEA may thus prove useful as a steroid-sparing agent in the management of inflammatory disorderssuch as SLE or rheumatoid arthritis. Further in vivo studies are indicated.
机译：骨质疏松症和相关的骨折是糖皮质激素使用的最常见且使人衰弱的并发症。需要使用没有糖皮质激素的有害骨骼作用的替代抗炎药。脱氢表雄酮（DHEA）对骨骼可能具有免疫调节作用以及积极作用。为了进一步了解作为类固醇保护剂的脱氢表雄酮（DHEA）的作用机理，我们研究并比较了地塞米松（DEX）和脱氢表雄酮（DHEA）对破骨细胞生成下游效应子途径的调节作用; RANKL / OPG和一系列炎症/促吸收细胞因子和受体，使用的是人类克隆性成骨细胞系。用DEX，DHEA和雄烯二酮（ANDI）处理细胞。过夜孵育后，通过实时PCR测定RANKL和OPG的mRNA表达。还使用人类细胞因子/生长因子和由268种细胞因子相关cDNA组成的受体基因阵列研究了DEX和DHEA对多种细胞因子的调节作用。为了确认某些基因表达的变化，通过ELISA测量了蛋白质的产生。 DEX增加了RANKL表达和RANKL / OPG比。与DHEA或ANDI共同治疗可逆转这种作用。包括IL-6，IL-4，IFN-γ，巨噬细胞抑制因子（MIF）在内的几种促炎/吸收性细胞因子不仅被DEX降低，还被DHEA下调。与DEX相反，DHEA不会导致生长因子的抑制，包括血管内皮生长因子（VEGF），成纤维细胞生长因子5（FGF-5），胰岛素样生长因子结合蛋白3（IGF-BP3）。 DHEA上调了先前记录的影响骨骼形成的几个新靶基因，例如Notch 2，胰岛素受体，凝血酶受体（PAR1）。数据表明，使用糖皮质激素可观察到DHEA具有免疫调节特性，而对骨骼重塑没有分解代谢作用。因此，DHEA可能被证明是类固醇保护剂，可用于治疗SLE或类风湿性关节炎等炎症性疾病。指出了进一步的体内研究。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号