Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Induction of transforming growth factor beta (TGF-beta) by the immunosuppressive drug cyclosporin A (CsA) in activated lymphocytes has been claimed to add to the renal pro-fibrotic effects of CsA. The aim of this study was to evaluate CsA-mediated TGF-beta induction in a larger number of lymphocyte preparations from different donors. Peripheral blood lymphocytes (PBL) were obtained from healthy blood donors. The cells were stimulated with phytohemagglutinin E (PHA) and phorbol ester (tetradecanoyl phorbol acetate, TPA) in the presence or absence of CsA. TGF-beta, interleukin-2 (IL-2) and cyclooxygenase-2 (Cox-2) mRNA were detected by Northern blot analysis or by real time reverse transcriptase-polymerase chain reaction (RT-PCR). TGF-beta and IL-2 protein were determined in the cellular supernatants by enzyme-linked immunosorbent assay. TGF-beta mRNA and protein were up-regulated when the cells were stimulated with PHA/TPA. Cyclosporin A at high concentrations (500 ng/mL) caused a transient increase in TGF-beta mRNA which was significant after 2 h. CsA did not induce sustained TGF-beta protein expression (24-72 h) in any of the preparations (n = 14), whereas the up-regulation of IL-2 mRNA and protein was prevented by CsA in the same preparations. Furthermore, up-regulation of Cox-2 mRNA was inhibited by CsA. Taken together, there was no evidence for TGF-beta as a clinically relevant mediator being induced by CsA in activated peripheral blood T-lymphocytes.
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PMID:Failure of cyclosporin A to induce transforming growth factor beta (TGF-beta) synthesis in activated peripheral blood lymphocytes. 1258 17

Equine endotoxaemia is an important cause of morbidity and mortality in horses caused by the interaction of bacterial lipopolysaccharide (LPS) with cells such as macrophages and vascular smooth muscle. In this study we isolated equine vascular smooth muscle from a variety of vessels and stimulated it with LPS and human interferon (hIFN)-gamma. Using reverse transcriptase polymerase chain reaction (rt-PCR) and Western blot analysis we show that cyclooxygenase-2 (COX-2) is readily expressed in equine vascular smooth muscle. Vascular smooth muscle cells produced prostaglandin E2 in response to LPS and hIFNgamma. Using similar approaches we saw very limited expression of inducible nitric oxide synthase (iNOS) in only one vascular smooth muscle preparation. LPS and IFNgamma caused translocation of the transcription factor nuclear factor kappa B (NfkappaB) to the nucleus in equine cells suggesting the limited iNOS production seen in our cells is not due to deficits in this signal transduction pathway. These data suggest that in equine vascular smooth muscle COX-2 and NfkappaB are likely to play important roles in the pathogenesis of equine endotoxaemia.
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PMID:Lipopolysaccharide and interferon gamma activate nuclear factor kappa B and induce cyclo-oxygenase-2 in equine vascular smooth muscle cells. 1289 62

The objective of this study was to determine whether cyclooxygenase-2 (COX-2) is up-regulated in the synovium of patients with carpal tunnel syndrome. Twenty patients were enrolled: 16 consecutive patients with carpal tunnel syndrome and four control patients (exploration for non-carpal tunnel syndrome-related wrist or forearm pathology). Clinical data (demographics, pertinent history, symptomatology) were obtained preoperatively. Flexor tenosynovial tissue was isolated from all patients and clinically graded as thin, intermediate, or thick. Histologic evaluation was conducted to rule out the presence of inflammatory cells. Immunohistochemical staining for COX-2 was performed. The immunohistochemical data were confirmed by reverse transcriptase-polymerase chain reaction analysis of COX-2 mRNA. Results showed that the majority of carpal tunnel syndrome specimens (88 percent) showed synovial hypertrophy compared with 0 percent of the controls (p < 0.05). Also, 69 percent of carpal tunnel syndrome specimens (11 of 16) versus 0 percent of controls (zero of four) stained positively for COX-2 (p < 0.05). Of the carpal tunnel syndrome patients, 91 percent of thick specimens versus 33 percent of intermediate specimens versus 0 percent of thin specimens showed COX-2 staining. The authors conclude that synovial hypertrophy is a prominent finding in carpal tunnel syndrome. COX-2 is up-regulated in the tenosynovium of patients with carpal tunnel syndrome, and this upregulation may correlate with the clinical grade of the tenosynovium. The role of COX-2 in carpal tunnel syndrome may be to mediate remodeling of pathologic tissue. To this end, it may be a potential therapeutic target for specific inhibition.
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PMID:COX-2 up-regulation in idiopathic carpal tunnel syndrome. 1466 24

Hepatocyte growth factor (HGF) overexpression is observed in experimental and clinical acute pancreatitis. Moreover, previous studies have shown that administration of HGF reduces pancreatic damage in experimental pancreatitis. The aim of our studies was to determine the role of cyclooxygenase-1 and cyclooxygenase-2 in the protective effect of HGF administration against caerulein-induced pancreatitis. Acute pancreatitis was induced in rats by infusion of caerulein. HGF was administered twice at the dose 10 microg/kg s.c. The activity of cyclooxygenase-1 and cyclooxygenase-2 was inhibited by resveratrol and rofecoxib, respectively (10 mg/kg). Immediately after cessation of caerulein or saline infusion, pancreatic blood flow, pancreatic cell proliferation, pancreatic prostaglandin E(2) generation, plasma lipase activity, plasma interleukin-1 beta and interleukin-10 concentration were measured and morphological signs of pancreatitis were examined. Expression of cyclooxygenase-1 and cyclooxygenase-2 mRNA transcripts was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). Cyclooxygenase protein production was analyzed by Western blot. Administration of HGF or caerulein alone, or their combination, was without effect on cyclooxygenase-1 mRNA expression in pancreatic tissue. Expression of cyclooxygenase-2 mRNA was increased by HGF and caerulein. The maximal increase in cyclooxygenase-2 mRNA expression was observed when HGF administration was combined with caerulein infusion. A similar effect was observed when we studied the influence of HGF and caerulein on pancreatic cyclooxygenase-2 production, as determined by Western blot. Administration of HGF without induction of acute pancreatitis increased pancreatic prostaglandin E(2) generation and plasma interleukin-10, and this effect was abolished by the cyclooxygenase-2 inhibitor, rofecoxib. Treatment with HGF, during the development of pancreatitis, increased the plasma interleukin-10 concentration and attenuated pancreatic damage, as evidenced by: (a) histological improvement of pancreatic integrity; (b) the partial reversal of the decrease in DNA synthesis and pancreatic blood flow; (c) the reduction in pancreatitis-evoked increase in plasma lipase and interleukin-1 beta. Administration of resveratrol and rofecoxib alone was without effect on the development of pancreatitis. Combination of rofecoxib with HGF reduced the HGF-evoked increase in plasma interleukin-10 concentration and pancreatic prostaglandin E(2) generation, and abolished the protective effect of HGF against pancreatic damage in pancreatitis. Resveratrol did not affect the protective effect of HGF. We conclude that: (1) HGF induces cyclooxygenase-2 but not cyclooxygenase-1 expression; (2) inhibition of cyclooxygenase-2 in HGF-treated rats decreases the release of anti-inflammatory interleukin-10, increases the production of pro-inflammatory interleukin-1 beta and reduces pancreatic blood flow; (3) cyclooxygenase-2 activity is necessary for the protective effect of HGF in acute pancreatitis.
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PMID:Inhibition of cyclooxygenase-2 reduces the protective effect of hepatocyte growth factor in experimental pancreatitis. 1475 15

Prostaglandin E(2) (PGE(2)) can have pro- or anti-inflammatory effects, depending on engagement of different PGE(2) receptor (EP) subtypes. The role of EPs in regulating autoimmune inflammation was studied in the murine arthritis/lupus model induced by pristane. Peritoneal macrophages were isolated (biomagnetic beads) from BALB/c, DBA/1, or C57BL/6 mice treated with pristane (intraperitoneally, 3 months earlier) or thioglycolate (3 days earlier) or with untreated controls. EPs, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) mRNA expression was examined by reverse transcriptase-polymerase chain reaction (RT-PCR). Cells were cultured unstimulated or stimulated with lipopolysaccharide (LPS) or LPS + interferon-gamma in combination with EP subtype-specific agonists. Tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-6 production was tested by enzyme-linked immunosorbent assay (culture supernatant) and flow cytometry. TNF-alpha mRNA levels also were examined. High levels of EPs (EP4/2>EP1>EP3), iNOS, and COX-2 mRNA were expressed in peritoneal macrophages from pristane-treated but not untreated or thioglycolate-treated mice (RT-PCR). TNF-alpha production was inhibited 50-70% at 2-24 h by EP4/2 agonists, whereas IL-6 was enhanced up to approximately 220%. TNF-alpha inhibition is mediated partly via the protein kinase A pathway and partly via IL-6. Intracellular TNF-alpha staining was inhibited 20% by EP4/2 agonists. TNF-alpha mRNA levels were inhibited 50-70% at 2-24 h, indicating that TNF-alpha inhibition was partly at the level of transcription. EP1/3 agonists had little effect. Synovial cells from mice with pristane-induced arthritis (DBA/1) also expressed EP2/4, and the EP2/4 agonist inhibited TNF-alpha production. PGE(2) can modulate inflammatory reactions via the EP2/4 receptor through its regulation of TNF-alpha and IL-6. Modification of EP signaling may be a new therapeutic strategy in inflammatory/autoimmune diseases.
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PMID:Prostaglandin E2 receptors EP2 and EP4 are up-regulated in peritoneal macrophages and joints of pristane-treated mice and modulate TNF-alpha and IL-6 production. 1507 56

We recently showed that zerumbone, a sesquiterpene found in subtropical ginger, suppresses colonic tumor marker formation in rats and induces apoptosis in colon cancer cell lines. In our present study, the anti-tumor initiating and promoting activities of zerumbone in mouse skin were evaluated using a conventional 2-stage carcinogenesis model. A single topical pretreatment to mouse skin (2 micromol) 24 hr before application of dimethylbenz[a]anthracene (0.2 micromol) markedly suppressed tumor incidence by 60% and the number of tumors by 80% per mouse. Repeated pretreatment (16 nmol) twice weekly during the post-initiation phase reduced the number of 12-O-tetradecanoylphorbol-13-acetate (TPA, 1.6 nmol)-induced tumors by 83% as well as their diameter by 57%. Multiple reverse transcriptase (RT) PCR experiments revealed that zerumbone (2 micromol) enhanced the mRNA expression level of manganese superoxide dismutase, glutathione peroxidase-1, glutathione S-transferase-P1 and NAD(P)H quinone oxidoreductase in the epidermis, but not that of cytochrome p450 1A1 or 1B1. Further, it diminished TPA-induced cyclooxygenase-2 protein expression and phosphorylation of extracellular signal-regulated kinase 1/2, while pretreatment(s), in either the priming or activation stage or both, reduced double TPA application-induced hydrogen peroxide formation and edema induction by 29% to 86%, respectively. Histologic examination revealed that pretreatment(s) with zerumbone suppressed leukocyte infiltration and reduced proliferating cell nuclear antigen-labeling indices. Together, our results indicate that zerumbone is a promising agent for the prevention of both tumor initiating and promoting processes, through induction of anti-oxidative and phase II drug metabolizing enzymes as well as attenuation of proinflammatory signaling pathways.
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PMID:Zerumbone, a sesquiterpene in subtropical ginger, suppresses skin tumor initiation and promotion stages in ICR mice. 1512 79

To examine how substance P (SP) is related with dental pulp inflammation, we examined the effects of SP on expression of genes for inflammatory factors in human dental pulp cell cultures. Using reverse transcriptase-polymerase chain reaction, we found that Prevotella intermedia lipopolysaccharide (LPS) induced expression of SP and SP-receptor mRNAs, and that somatostatin inhibited the LPS-induced expression of SP mRNA. We also found that SP enhanced LPS-induced stimulation of NF-kappaB binding activity. In addition, SP induced expression of cyclooxygenase-2 and interleukin-10 receptor mRNAs. In contrast, SP inhibited expression of interferon-gamma receptor mRNA. These results suggest that SP may play a regulatory role in the immunological response of dental pulp tissue to pathogenic bacteria.
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PMID:Substance P enhances expression of lipopolysaccharide-induced inflammatory factors in dental pulp cells. 1550 7

Previously, wogonin (5,7-dihydroxy-8-methoxyflavone) was found to suppress proinflammatory enzyme expression including cyclooxygenase-2 (COX-2), contributing to in vivo anti-inflammatory activity against skin inflammation. However, the detailed effect on each skin cell type has not been understood. Therefore, present investigation was carried out to find the effect of wogonin on inflammation associated gene expression from skin fibroblasts in culture using reverse transcriptase-polymerase chain reaction. As a result, it was found that wogonin (10-100 microM) clearly down-regulated COX-2 expression from NIH/3T3 cells treated with 12-O-tetradecanoylphorbol 13-acetate, interleukin-1beta or tumor necrosis factor-alpha. But, the expression levels of COX-1, interleukin-1beta and fibronectin were not significantly affected. This finding was well correlated with significant reduction of prostaglandin E2 (PGE2) production by wogonin. As a comparison, NS-398 (selective cyclooxygenase 2 inhibitor) did not suppress COX-2 expression and other gene levels, while PGE2 production was potently reduced at 0.1-10 microM. All these results suggest that COX-2 down-regulation of skin fibroblasts may be, at least in part, one of anti-inflammatory mechanisms of wogonin against skin inflammation.
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PMID:Suppression of cyclooxygenase-2 expression of skin fibroblasts by wogonin, a plant flavone from Scutellaria radix. 1558

Cyclooxygenase-2 (COX-2) displays anti-apoptotic functions related to angiogenesis or blocking of bcl-2 functions. COX-2 overexpression has been found in various human malignancies, including esophageal squamous cell carcinoma (ESCC). The present study examined correlations between expression of COX-2 mRNA and ESCC responses to chemoradiotherapy (CRT). Expression of COX-2 mRNA obtained from 29 biopsy specimens before CRT was quantified using reverse transcriptase-polymerase chain reaction (RT-PCR) using Sybr Green I on the Roche LightCycler system. CRT comprised 5-fluorouracil plus cisplatin and 40 Gy of radiation. Mean COX-2 mRNA score was significantly higher in tumors (1222) than in normal epithelium (50; p=0.05). Expression of COX-2 mRNA was high in 14 patients, low in 8 and absent in 7. The effective response to CRT was achieved in 18 patients. Mean COX-2 mRNA score was significantly higher in ineffective cases (2910) than in effective cases (190; p<0.05). CRT was more effective in patients with low COX-2 mRNA expression than in those with high expression. COX-2 mRNA expression in biopsy specimens was closely related to CRT effectiveness. Examination of COX-2 mRNA expression is useful for predicting the effect of CRT in patients with ESCC.
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PMID:Predictive value of COX-2 for the effect of chemoradiotherapy on esophageal squamous cell carcinoma. 1575 44

Since both endothelin-1 (ET-1) and aldosterone have been shown to induce expression of several pro-inflammatory genes, including cyclooxygenase-2 (COX-2), in the vasculature as a cardiovascular risk hormone, the present study was undertaken to examine the effects of ET-1 and aldosterone on COX-2 gene expression as measured by a real-time reverse transcriptase-polymerase chain reaction in aortic endothelial cells. Treatment with ET-1(10 M) markedly upregulated COX-2 mRNA levels in rat endothelial cells, whereas aldosterone (10 M) did not show any effect. The ET-1-induced COX-2 upregulation was inhibited by pretreatment with a non-selective endothelin receptor antagonist (TAK044), a protein kinase C inhibitor (GF109203X), and a MEK inhibitor (PD98059). Furthermore, ET-1 increased intracellular reactive oxygen species generation as estimated by the measurement of dichlorofluorescein fluorescence, whose effect was blocked by a COX-2 inhibitor (NS398). Our data show that ET-1 induces COX-2 upregulation in rat endothelial cells via a protein kinase C-dependent and extracellular signal-regulated kinase-dependent pathway, which may largely contribute to the generation of intracellular reactive oxygen species.
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PMID:Endothelin-1 induces cyclooxygenase-2 expression and generation of reactive oxygen species in endothelial cells. 1583 13


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