Proinflammatory cytokines regulate human glucocorticoid receptor gene expression and lead to the accumulation of the dominant negative beta isoform: a mechanism for the generation of glucocorticoid resistance.

Webster JC; Oakley RH; Jewell CMCidlowski JA

首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Proinflammatory cytokines regulate human glucocorticoid receptor gene expression and lead to the accumulation of the dominant negative beta isoform: a mechanism for the generation of glucocorticoid resistance.

【24h】

Proinflammatory cytokines regulate human glucocorticoid receptor gene expression and lead to the accumulation of the dominant negative beta isoform: a mechanism for the generation of glucocorticoid resistance.

机译：Proinflammatory cytokines regulate human glucocorticoid receptor gene expression and lead to the accumulation of the dominant negative beta isoform: a mechanism for the generation of glucocorticoid resistance.

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相关主题

摘要

Inflammatory responses in many cell types are coordinately regulated by the opposing actions of NF-kappaB and the glucocorticoid receptor (GR). The human glucocorticoid receptor (hGR) gene encodes two protein isoforms: a cytoplasmic alpha form (GRalpha), which binds hormone, translocates to the nucleus, and regulates gene transcription, and a nuclear localized beta isoform (GRbeta), which does not bind known ligands and attenuates GRalpha action. We report here the identification of a tumor necrosis factor (TNF)-responsive NF-kappaB DNA binding site 5' to the hGR promoter that leads to a 1.5-fold increase in GRalpha mRNA and a 2.0-fold increase in GRbeta mRNA in HeLaS3 cells, which endogenously express both GR isoforms. However, TNF-alpha treatment disproportionately increased the steady-state levels of the GRbeta protein isoform over GRalpha, making GRbeta the predominant endogenous receptor isoform. Similar results were observed following treatment of human CEMC7 lymphoid cells with TNF-alpha or IL-1. The increase in GRbeta protein expression correlated with the development of glucocorticoid resistance.

著录项

来源
《Proceedings of the National Academy of Sciences of the United States of America》 |2001年第12期|6865-6870|共6页
作者
Webster JC; Oakley RH; Jewell CMCidlowski JA;
展开▼
作者单位

Molecular Endocrinology Group, Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.;

artners.org;

展开▼
收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Cytokines; Gene Expression Regulation; Glucocorticoids; NF-kappa B; Receptors; Glucocorticoid; 细胞活素类; 基因表达调控; 糖皮质激素类; NF-κB; 受体; 糖皮质激素;

Proinflammatory cytokines regulate human glucocorticoid receptor gene expression and lead to the accumulation of the dominant negative beta isoform: a mechanism for the generation of glucocorticoid resistance.

摘要

著录项

相关主题

期刊订阅