Abstract：
:Bronchial epithelial cells play an important role in amplifying and perpetuating airway inflammation and may be a target for inhaled steroids. We have characterized glucocorticoid receptors in primary human bronchial epithelial cells. Northern and western blot analyses demonstrated the expression of glucocorticoid receptor mRNA and protein, respectively, in primary bronchial epithelial cells. The activity of these receptors was shown using a radioligand binding assay. High-affinity binding with pharmacological specificity was demonstrated for [3H]dexamethasone. The equilibrium dissociation constant (Kd) and density of binding sites (Bmax) for [3H]dexamethasone determined from saturation isotherms were 4.4 nM x/divided by 0.95 (SEM) and 30.1 fmol/mg protein +/-6.4 (SEM). Glucocorticoid receptors were activated by dexamethasone as assessed using a glucocorticoid-responsive reporter plasmid, pTAT3-CAT. Transfection of primary human bronchial epithelial cells with this reporter plasmid resulted in 35-fold activation of transcription following dexamethasone stimulation (10(-6) M). The glucocorticoid receptor antagonist RU-486 (mifepristone) significantly counteracted the effect of dexamethasone on glucocorticoid receptor activation, indicating that the dexamethasone effect is specific and is mediated through the glucocorticoid receptor. In summary, our study demonstrated that primary cultures of human bronchial epithelial cells possess glucocorticoid receptors that function as a ligand-activated transcriptional regulator. The presence of glucocorticoid receptors confers their responsiveness to glucocorticoids and indicates that the airway epithelium may be a target for the anti-inflammatory effects of inhaled steroids.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
LeVan TD,Babin EA,Yamamura HI,Bloom JWdoi
10.1016/s0006-2952(99)00008-8subject
Has Abstractpub_date
1999-05-01 00:00:00pages
1003-9issue
9eissn
0006-2952issn
1873-2968pii
S0006-2952(99)00008-8journal_volume
57pub_type
杂志文章abstract：:In a variety of malignant cells the prostate-apoptosis-response-gene-4 (Par-4) induces increased sensitivity towards chemotherapeutic agents by down-regulating anti-apoptotic B-cell lymphoma-gene 2 (Bcl-2). Hypothesizing that Par-4 also influences apoptosis in myeloid cell lines, we tested this hypothesis by stably tr...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
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doi：10.1016/s0006-2952(01)00900-5
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doi：10.1016/0006-2952(93)90553-9
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journal_title：Biochemical pharmacology
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pub_type： 杂志文章
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journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
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更新日期：2010-09-01 00:00:00
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journal_title：Biochemical pharmacology
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