• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>American Journal of Physiology >Glucocorticoid reamplification within cells intensifies NF-κB and MAPK signaling and reinforces inflammation in activated preadipocytes
【24h】

Glucocorticoid reamplification within cells intensifies NF-κB and MAPK signaling and reinforces inflammation in activated preadipocytes

机译：细胞内糖皮质激素的扩增增强了NF-κB和MAPK信号传导并增强了活化前脂肪细胞中的炎症

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

Increased expression and activity of the intracellular glucocorticoid- reactivating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) contribute to dysfunction of adipose tissue. Although the pathophysiological role of 11β-HSD1 in mature adipocytes has long been investigated, its potential role in preadipocytes still remains obscure. The present study demonstrates that the expression of 11β-HSD1 in preadipocyte-rich stromal vascular fraction (SVF) cells in fat depots from ob/ob and diet-induced obese mice was markedly elevated compared with lean control. In 3T3-L1 preadipocytes, the level of mRNA and reductase activity of 11β-HSD1 was augmented by TNF-α, IL-1β, and LPS, with a concomitant increase in inducible nitric oxide synthase (iNOS), monocyte chemoattractant protein-1 (MCP-1), or IL-6 secretion. Pharmacological inhibition of 11β-HSD1 and RNA interference against 11β-HSD1 reduced the mRNA and protein levels of iNOS, MCP-1, and IL-6. In contrast, overexpression of 11β-HSD1 further augmented TNF-α-induced iNOS, IL-6, and MCP-1 expression. Moreover, 11β-HSD1 inhibitors attenuated TNF-α-induced phosphorylation of NF-κB p65 and p38-, JNK-, and ERK1/2-MAPK. Collectively, the present study provides novel evidence that inflammatory stimuli-induced 11β-HSD1 in activated preadipocytes intensifies NF-κB and MAPK signaling pathways and results in further induction of proinflammatory molecules. Not limited to 3T3-L1 preadipocytes, we also demonstrated that the notion was reproducible in the primary SVF cells from obese mice. These findings highlight an unexpected, proinflammatory role of reamplified glucocorticoids within preadipocytes in obese adipose tissue.
机译：细胞内糖皮质激素再激活酶11β-羟基类固醇脱氢酶1（11β-HSD1）的表达和活性增加，导致脂肪组织功能障碍。尽管长期以来已经研究了11β-HSD1在成熟脂肪细胞中的病理生理作用，但其在前脂肪细胞中的潜在作用仍然不清楚。本研究表明，与瘦对照相比，ob / ob和饮食诱导的肥胖小鼠的脂肪仓库中富含前脂肪细胞的基质血管分数（SVF）细胞中11β-HSD1的表达明显升高。在3T3-L1前脂肪细胞中，TNF-α，IL-1β和LPS增强11β-HSD1的mRNA和还原酶活性，同时诱导型一氧化氮合酶（iNOS），单核细胞趋化蛋白1（ MCP-1）或IL-6分泌。药理抑制11β-HSD1和RNA干扰11β-HSD1降低了iNOS，MCP-1和IL-6的mRNA和蛋白质水平。相反，11β-HSD1的过表达进一步增强了TNF-α诱导的iNOS，IL-6和MCP-1的表达。此外，11β-HSD1抑制剂减弱了TNF-α诱导的NF-κBp65和p38-，JNK-和ERK1 / 2-MAPK的磷酸化。总的来说，本研究提供了新的证据，即激活的前脂肪细胞中炎症刺激诱导的11β-HSD1增强了NF-κB和MAPK信号通路，并导致进一步诱导促炎分子。不限于3T3-L1前脂肪细胞，我们还证明了该概念在肥胖小鼠的原代SVF细胞中可重现。这些发现突显了肥胖脂肪组织中前脂肪细胞内糖皮质激素增高的预料不到的促炎作用。

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