Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Platelet-derived growth factor (B) (PDGF(B)) from alveolar macrophages is thought to play a central role in orchestrating the fibrotic response. Because corticosteroids are widely used in the treatment of patients with lung fibrosis, we asked whether corticosteroids modulated PDGF(B) gene activation in macrophages. PDGF(B) mRNA in alveolar macrophages obtained from smokers was increased after culture in the presence of dexamethasone (P less than 0.05), interferon-gamma (IFN-gamma) (P less than 0.05), or both in combination (P less than 0.05). Dexamethasone did not alter the abundance of mRNA encoding transforming growth factor-beta (TGF-beta), but did decrease the mRNA of early growth response gene 2 (EGR2). These initial experiments required large numbers of cells and thus were performed on macrophages from smokers. The results were reproduced when PDGF(B) mRNA abundance in macrophages from healthy nonsmoking volunteers was measured by the reverse-transcriptase polymerase chain reaction (RT-PCR). There was an increase in PDGF(B) mRNA in macrophages from nonsmokers after stimulation with dexamethasone alone (P less than 0.05) or in combination with IFN-gamma (P less than 0.05). To provide adequate cell numbers for kinetic and dose-response studies, the in vitro model of phorbol ester (TPA)-induced differentiation of HL60 cells to macrophage-like cells was used. In these cells, dexamethasone caused a 20-fold increase in the abundance of PDGF(B) mRNA, which was concentration and time dependent but not associated with changes in TGF-beta or EGR2 mRNA. This study suggests that in addition to their anti-inflammatory effects, corticosteroids may also increase the abundance of PDGF(B) mRNA.
 ...
PMID:Dexamethasone-induced increase in platelet-derived growth factor (B) mRNA in human alveolar macrophages and myelomonocytic HL60 macrophage-like cells. 149 7

The effects of dexamethasone on the growth of four human multiple myeloma cell lines were studied. In addition, the effects on the expression of interleukin-6 (IL-6) and IL-6 receptor (IL-6R) genes were investigated by the use of reverse-transcriptase polymerase chain reaction. Dexamethasone (Dex) concentrations of 10(-7) to 10(-6) mol/L inhibited IL-6 gene expression in three of four cell lines studied, whereas the higher concentration of the hormone inhibited also IL-6R gene expression. Dex effects were modulated through the glucocorticoid receptor (GR). Dex treatment resulted in killing of sensitive cells associated with DNA fragmentation, which could be reversed by concomitant treatment with IL-6. The reversal of Dex-mediated effects by IL-6 did not result from an inhibition of GR function as measured by receptor nuclear translocation or Dex-regulated reporter gene function. These results indicate that blockage of the IL-6 signaling pathway is essential for effective myeloma cell kill by Dex.
 ...
PMID:Interleukin-6 prevents dexamethasone-induced myeloma cell death. 794 78

Although both rat cardiac nonmyocytes (mostly fibroblasts) and cardiomyocytes have a functional angiotensin II (AngII) receptor, the regulation mechanism of its subtype expression in the rat heart remains unknown. In this study, by using a binding assay and a competitive reverse-transcriptase polymerase chain reaction, we examined the regulation of AngII types 1a and 1b (AT1a-R and AT1b-R) and type 2 receptor (AT2-R) expression in embryonal day 19 (E19) and neonatal (1-d) rat cardiac fibroblasts and cardiomyocytes. The number of AT2-R in E19 fibroblasts was dramatically decreased (from 305 to 41 fmol/mg protein) in 1-d fibroblasts, whereas that of AT1-R and the mRNA levels remained unchanged. The ratio of AT1a-R to AT1b-R mRNA in both E19 and 1-d fibroblasts was 9:1. The number of AT2-R in E19 cardiomyocytes was also significantly decreased (from 178 to 87 fmol/mg protein) in 1-d cardiomyocytes, whereas the magnitude was less prominent compared with that in fibroblasts. AT1-R expression remained unaltered in E19 and 1-d cardiomyocytes. In E19 and 1-d cardiomyocytes, the AT1b-R mRNA level was 1.5-fold higher than that of AT1a-R mRNA. Dexamethasone induced significant increases in AT1a-R mRNA (2.1-fold) and numbers (1.8-fold) without changing the affinity, whereas neither AT1b-R mRNA nor the number of AT2-R was affected by dexamethasone. The AT1a-R gene transcription rate, determined by means of a nuclear run-off assay, was increased (2-fold) by dexamethasone. The half-life of AT1a-R mRNA (18 h) was unchanged by dexamethasone. These data indicate that AngII receptor subtype expression in the rat heart is regulated in a cell- and subtype-specific manner.
 ...
PMID:Differential gene expression and regulation of angiotensin II receptor subtypes in rat cardiac fibroblasts and cardiomyocytes in culture. 816 61

The regulation of the expression of beta-adrenoceptor (beta-ARs) is not thoroughly understood. We demonstrate that the rat heart cell-line H9c2 expresses both beta 1- and beta 2-ARs. In radioligand-binding experiments, the maximal binding capacity of (-)-[125I]-iodocyanopindolol was determined as 18 +/- 0.6 fmol/mg of protein with a KD of 35.4 +/- 4.1 pM. Competitive radioligand-binding experiments with subtype-specific beta-antagonists reveal a subtype ratio of beta 1- to beta 2-ARs of 29%: 71%. With competitive reverse-transcriptase PCR we found beta 2-mRNA to be up to 1600 times more frequent than beta 1-mRNA. Treatment of the H9c2 cell-line with the beta-adrenergic agonist (-)-isoproterenol (10(-6) M), the antagonist (-)-propranolol (10(-6) M) and the glucocorticoid dexamethasone (500 nM) induces regulatory effects on both the beta-AR protein and mRNA level. Isoproterenol treatment leads to down-regulation of the total receptor number by 56 +/- 4%, due to a decrease in beta 2-ARs, while maintaining the beta 1-AR number constant. On the transcription level, both beta 1-and beta 2-mRNAs are decreased by 30% and 42% respectively. mRNA stability measurements reveal a reduced half-life of beta 2-mRNA from 9.3 h to 6.5 h after isoproterenol treatment. Incubation of cells with (-)-propranolol does not affect the amounts of beta-ARs and their mRNAs. Dexamethasone induces a 1.8 +/- 0.2-fold increase in beta-AR number over the basal level as well as a 1.9 +/- 0.2-fold increase in the amount of beta 2-mRNA. Because the half-life of beta 2-mRNA was unaffected by dexamethasone, the increased beta 2-mRNA level must be due to an enhanced transcription rate. The beta 1-mRNA levels are unchanged during dexamethasone-incubation of the cells. Our data clearly demonstrate that treatment of H9c2 rat heart cells with isoproterenol and dexamethasone induces alterations in the level of RNA stability as well as gene transcription, leading to altered receptor numbers.
 ...
PMID:Regulation of beta-adrenoceptor density and mRNA levels in the rat heart cell-line H9c2. 876 Mar 84

Nontraumatic osteonecrosis is related to alcohol and glucocorticoid with unknown pathogenesis. Increased adipogenesis decreases bone morphogenetic protein 2 (BMP2) gene expression after glucocorticoid treatment. Lovastatin enhances BMP2 gene expression in rodents, reverses the effects of glucocorticoids on bone, and prevents glucocorticoid-induced osteonecrosis in chickens and humans. We hypothesized patients with osteonecrosis are more susceptible to glucocorticoid treatment than patients without osteonecrosis. Marrow stromal cell cultures from 14 patients with osteonecrosis, and 10 patients without osteonecrosis were treated with dexamethasone (0.1 micromol/L), lovastatin (1 micromol/L), or combined treatment. BMP2 and osteocalcin gene expression were evaluated by reverse-transcriptase polymerase chain reaction and real-time polymerase chain reaction. The suppression of BMP2 by dexamethasone was more pronounced and the enhancement by lovastatin was less pronounced in the osteonecrosis group. Dexamethasone suppressed osteocalcin in the osteonecrosis group. Among the subgroups of osteonecrosis, suppression of BMP2 and osteocalcin by dexamethasone occurred in glucocorticoid-induced osteonecrosis group. Our data suggest individuals who are more susceptible to a glucocorticoid-induced decreases in BMP2 and osteocalcin gene expression are more likely to have osteonecrosis, especially glucocorticoid-induced osteonecrosis.
 ...
PMID:Osteogenic gene expression decreases in stromal cells of patients with osteonecrosis. 1701 24

Glucocorticoids are often used in veterinary cancer patients because of their anti-inflammatory actions, appetite-stimulating effects, ability to decrease nausea and vomiting associated with some chemotherapy agents, and, in some instances, for their cytotoxic actions on susceptible tumour cells. Veterinary oncologists may not consider the possibility that the use of glucocorticoids may adversely affect response to chemotherapy. There is evidence that glucocorticoids can up-regulate the expression of multidrug resistance genes in some tissues. Whether or not glucocorticoid-induced expression of multidrug resistance proteins occurs in tumour cells is not presently known. The purpose of this study was to determine if dexamethasone induces P-glycoprotein (P-gp) or multidrug resistance-related protein 1 (MRP1) in tumour cell lines. A canine osteosarcoma cell line (OS2.4) and a human myeloid leukaemia cell line 60 (HL60) were treated in culture with dexamethasone. The presence of a glucocorticoid receptor was confirmed in both cell lines by reverse-transcriptase polymerase chain reaction. Western blots for P-gp and MRP1 expression were performed on vehicle-treated and dexamethasone-treated cells. Sensitivity towards several chemotherapeutic drugs (cisplatin (cis-diamminedichloroplatinum), doxorubicin, methotrexate and vincristine) was determined by 3-(4,5-dimthylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. While dexamethasone treatment of OS2.4 cells increased the resistance to cisplatin and methotrexate, an increase in P-gp or MRP1 expression was not observed. Dexamethasone-treated HL60 cells did not develop chemoresistance and did not show increased expression of P-gp or MRP1.
 ...
PMID:Dexamethasone treatment of a canine, but not human, tumour cell line increases chemoresistance independent of P-glycoprotein and multidrug resistance-related protein expression. 1937 18