主页 > 医学前沿 >
【文摘发布】地塞米松对小梁细胞吞噬功能的抑
Zhang X, Ognibene CM, Clark AF, Yorio T.
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA.
Glucocorticoid treatment can lead to the development of glaucomatous ocular hypertension and a secondary open-angle glaucoma due to increased aqueous humor outflow resistance that is associated with morphological and biochemical changes in the trabecular meshwork (TM). The cellular responses of glucocorticoids are achieved by binding to the glucocorticoid receptor alpha (GRalpha), a ligand-activated transcription factor. An alternatively spliced variant, glucocorticoid receptor beta (GRbeta), has dominant negative activity on GRalpha and has been implicated in a variety of steroid-resistant diseases. We previously showed that GRbeta can block dexamethasone (DEX) responsiveness in TM cells. TM cells are actively phagocytic and function in the removal of debris, pigment and other materials from the aqueous outflow drainage pathway. A decrease in phagocytic activity has been proposed in the pathogenesis of glaucoma and glucocorticoid-induced glaucoma. In this study, we investigated the effect of DEX and GRbeta on phagocytosis in normal and glaucomatous TM cells. Human transformed normal NTM-5 and primary normal NTM174-00 cells, which express relatively high amounts of GRbeta, and transformed glaucomatous GTM-3 and primary glaucomatous GTM520-05 cells, which have lower GRbeta expression, were treated with 100 nM DEX or vehicle control for 24h. NTM cells also were transfected with a control or GRbeta expression plasmid to examine the effect of GRbeta on phagocytic activity. The cells were incubated with Alexa 488 conjugated Staphylococcus aureus bioparticles opsonized with rabbit IgG for 1h, followed by fixation and incubation with Alexa 633 conjugated goat anti-rabbit IgG to distinguish ingested from extracellular bioparticles. DAPI nuclear staining was used to quantify cell numbers. Cells and bioparticles were visualized by confocal microscopy. We found that NTM-5 cells ingested more bioparticles than GTM-3 cells. DEX treatment significantly decreased the phagocytosis of bioparticles in NTM-5 and GTM-3 cells, while GTM-3 cells were more responsive to DEX, compared to NTM-5 cells. In primary cell culture, NTM174-00 also engulfed more bioparticles than GTM520-05 cells. DEX treatment significantly decreased the phagocytic activity in GTM520-05, but not in NTM174-00 cells. Transient transfection of pCMX-hGRbeta plasmid increased the expression of GRbeta and consequently maintained the phagocytotic activity of NTM-5 cells in the presence of DEX. Our data demonstrated that the expression level of GRbeta in TM cells can regulate DEX-induced suppression of phagocytotic activity. The lower expression of GRbeta in glaucomatous TM cells may contribute to the altered phagocytic function of TM cells, and may lead to the increased aqueous humor outflow resistance mediated by glucocorticoids.
PMID: 17126833 [PubMed - indexed for MEDLINE] 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领 Exp Eye Res. 2007 Feb;84(2):275-84. Epub 2006 Nov 28.
题目：Dexamethasone inhibition of trabecular meshwork cell phagocytosis and its modulation by glucocorticoid receptor beta.
地塞米松对小梁网细胞吞噬功能的抑制作用和糖皮质激素受体-β对它的调节
作者：Zhang X, Ognibene CM, Clark AF, Yorio T.
作者单位：Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA.
文摘：Glucocorticoid treatment can lead to the development of glaucomatous ocular hypertension and a secondary open-angle glaucoma due to increased aqueous humor outflow resistance that is associated with morphological and biochemical changes in the trabecular meshwork (TM).
激素可引起小梁网在形态学和生化学上发生改变，使房水流出阻力增加，从而导致激素性高眼压和继发性开角性青光眼。
The cellular responses of glucocorticoids are achieved by binding to the glucocorticoid receptor alpha (GRalpha), a ligand-activated transcription factor.
糖皮质激素通过与配体依赖转录因子糖皮质激素受体-α（GRα）结合来发挥作用。
An alternatively spliced variant, glucocorticoid receptor beta (GRbeta), has dominant negative activity on GRalpha and has been implicated in a variety of steroid-resistant diseases.
GRβ由GR基因的同一转录产物通过另一种剪切方式产生，在许多激素抵抗性疾病的研究中显示它对GRα的功能有拮抗作用。
We previously showed that GRbeta can block dexamethasone (DEX) responsiveness in TM cells.
在前期研究中我们已经发现GRβ可以阻断地塞米松对小梁网细胞的作用。
TM cells are actively phagocytic and function in the removal of debris, pigment and other materials from the aqueous outflow drainage pathway.
阅读本文的人还阅读：
作者:admin@医学,生命科学 2010-10-07 05:11
医学,生命科学网