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)

Indoor air pollutants may cause inflammatory changes of the airways and adjacent pulmonary tissue. After phagocytosis of inhaled particles alveolar macrophages (AM) release chemotactic mediators capable of attracting inflammatory cells into the lung tissue. To evaluate these mechanisms further peripheral blood mononuclear cells (PBMNC) and human AM (freshly recovered from the lower respiratory tract) were exposed to the indoor particles Soot FR 101 and Printex 90, the asbestos fiber Chrysotile B, and titanium dioxide (TiO2) at concentrations of 10 or 50 microg/10(6) cells for up to 8 h. The migration of granulocytes into the conditioned supernatants of AM and PBMNC was quantified by chemotaxis assay in a Boyden chamber. Granulocyte migration increased by 42.3 +/- 25.8% (Chrysotile B), 64. 6 +/- 18.3% (FR 101), 74.2 +/- 16.5% (P 90), and 86.7 +/- 25.6% (TiO2) in AM-conditioned supernatants (p < 0.05). Qualitative, Interleukin (IL)-8 specific reverse transcriptase-polymerase chain reaction was performed after exposure of AM or PBMNC to Chrysotile B, FR 101, P 90, and TiO2 at concentrations of 10 and 50 microg/10(6) cells for 90 min. Each of the tested particles caused an increase in IL-8-specific mRNA expression of AM or PBMNC after particle exposure compared with the unexposed control. To find out if IL-8, the most powerful granulocyte chemokine, is involved, supernatants were preincubated with anti-IL-8. Granulocyte migration decreased by up to 35 +/- 15% (50 ng/ml anti-IL-8) and 41.5 +/- 16% (100 ng/ml anti-IL-8) (p < 0.0625) in AM-conditioned supernatants. Pretreatment of the granulocytes with human IL-8 decreased by up to 59 +/- 18% (10 ng/ml) (p < 0.0625) in AM-conditioned supernatants. Similar reaction patterns were observed using anti-IL-8-pretreated supernatants of particle-exposed PBMNC. In conclusion, indoor air pollutants may promote inflammatory changes in the lung via IL-8 release by alveolar macrophages.
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PMID:Indoor air pollutants stimulate interleukin-8-specific mRNA expression and protein secretion of alveolar macrophages. 983 30

N-(trifluoromethylphenyl)-2-cyano-3-hydroxy-crotonic acid amide (A77 1726), the physiologically active metabolite of leflunomide, has been described to exert antiproliferative effects in vitro and anti-inflammatory actions in several animal models. Currently, its use is being evaluated in clinical trials in psoriasis, which is characterized by epidermal hyperproliferation and infiltration of inflammatory cells. We studied the effects of A77 1726 on growth and gene expression in cultured epidermal cells by 5-bromo-2'-deoxy-uridine (BrdU) incorporation, reverse transcriptase-polymerase chain reaction (RT-PCR), Northern blot hybridizations and flow cytometry. A77 1726 inhibited epidermal proliferation at concentrations above 5 microM after 24 hr. However, the cells were still fully viable at a concentration of 100 microM. The drug caused a dose-dependent reduction in the mRNA level of the type A receptor for the proinflammatory cytokine interleukin-8 (IL-8-RA) and, in contrast, induced gene expression of the receptor for the anti-inflammatory cytokine IL-10 (IL-10R) at the mRNA and protein levels. In addition, the mRNA and protein levels of the p53 gene, which is a negative cell cycle regulator, were up-regulated by A77 1726. These data suggest that A77 1726 exerts its anti-inflammatory action via the modulation of epidermal gene expression.
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PMID:Differential modulation of pro- and anti-inflammatory cytokine receptors by N-(4-trifluoromethylphenyl)-2-cyano-3-hydroxy-crotonic acid amide (A77 1726), the physiologically active metabolite of the novel immunomodulator leflunomide. 1007 46

Flavonoids isolated from citrus were evaluated for their ability to affect the inflammation response through suppression of cytokine expression by human monocytes. Several polymethoxylated flavones inhibited lipopolysaccharide-induced monocyte expression of tumor necrosis factor (TNFalpha). Subsequent studies centered on the compound 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF) which produced the highest inhibition (IC50 = 5 microM). HMF was also a potent inhibitor of macrophage inflammatory protein-1alpha (MIP-1alpha) and interleukin-10 (IL-10) production, but not of IL-1beta, IL-6, or IL-8 production. Suppression of TNFalpha production was at the level of mRNA induction as determined by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). HMF was also a potent inhibitor of human phosphodiesterase activity and was shown to induce a substantial elevation of cAMP levels in monocytes. The similarity of these results to the inhibition profile of the known phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, suggests that the polymethoxylated flavones inhibit cytokine production in part by suppression of phosphodiesterase activity. The ability of HMF to also inhibit IL-10 production suggests the additional existence of a phosphodiesterase-independent mechanism for this compound.
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PMID:Polymethoxylated flavones derived from citrus suppress tumor necrosis factor-alpha expression by human monocytes. 1009 54

Chemokines play an important role in the selective movement of leucocytes into inflammatory areas and they also activate various cells in inflamed tissues. However, it is unclear which cells are the main sources of chemokines in actual inflammatory diseases, even though both mononuclear cells and non-inflammatory resident cells are able to produce chemokines in vitro and the former cells are also the main target of chemokines. To clarify the roles of chemokines that are produced by mononuclear cells in AD, we measured levels in vivo of mRNA for IL-8 and MIP-1 alpha, as well as the level of regulated upon activation normal T cell expressed and secreted (RANTES) mRNA in freshly isolated peripheral blood mononuclear cells from patients with AD. We compared the results with those from psoriatic patients, and patients without AD who were suffering from other cutaneous diseases and eosinophilia. Levels of mRNAs were determined by semiquantitative reverse transcriptase-polymerase chain reactions. Levels of IL-8 and MIP-1 alpha mRNA were elevated not only in atopic patients but also in non-atopic patients with inflammatory skin disease associated with eosinophilia, compared with levels in psoriatic patients and healthy controls. Levels of RANTES mRNA were similar in atopic patients but they were lower in the other two groups of patients when compared with levels in healthy controls. In atopic patients, the levels of both IL-8 and MIP-1 alpha mRNAs but not of RANTES mRNA decreased with improvements in symptom scores after therapy. These findings suggest that mononuclear cells are not only the target of chemokines but might also play an important role in the pathogenesis of AD by producing IL-8 and MIP-1 alpha.
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PMID:Increased levels in vivo of mRNAs for IL-8 and macrophage inflammatory protein-1 alpha (MIP-1 alpha), but not of RANTES mRNA in peripheral blood mononuclear cells of patients with atopic dermatitis (AD). 1044 53

Our goal was to determine the effect of transdermal nicotine on cytokine and mucin gene transcription in ulcerative colitis (UC). Sixty-four nonsmoking patients with active UC were randomly assigned to transdermal nicotine (maximum dose 22 mg/day) or placebo for 4 weeks. Clinical assessment and colonic mucosal biopsies were obtained at entry and after 4 weeks. Inflammatory and immunoregulatory cytokines were assessed by qualitative reverse transcriptase-polymerase chain reaction (RT-PCR). Based on this initial screen. IL-8 mRNA levels were measured by RT-competitive PCR. MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, and MUC6 mRNA concentrations were measured by quantitative dot blot analysis. Cytokine mRNA expression, except for IL-8, was similar in all patients. IL-8 mRNA levels were significantly decreased in the colonic mucosa of nicotine-treated patients who improved (p = 0.04). IL-8 mRNA values were similar before and after treatment in nonresponding nicotine-treated patients and in all placebo-treated patients. Mucin gene expression was similar in all patient groups. Beneficial effects of transdermal nicotine in active UC may result from decrease of IL-8 expression at the transcriptional level. Transdermal nicotine has no effect on mucin gene transcription.
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PMID:Transdermal nicotine decreases mucosal IL-8 expression but has no effect on mucin gene expression in ulcerative colitis. 1045 73

Coronary arteriosclerosis is an underlying condition in acute myocardial infarction (AMI), unstable angina pectoris (UAP) and stable angina pectoris (SAP), and is also related to restenosis (RS) following coronary intervention. To investigate the pathogenesis of this condition, a quantitative reverse transcriptase polymerase chain reaction was used to determine relative levels of mRNA for interleukin (IL)-1beta, IL-6, IL-8, transforming growth factor beta (TGF-beta), intercellular adhesion molecule (ICAM)-1, E-selectin and vascular cell adhesion molecule (VCAM)-1 using directional coronary atherectomy (DCA) specimens. Eleven patients with AMI, 7 with UAP, 10 with SAP and 6 with RS following a previous coronary intervention underwent DCA. The mRNA intensity for each molecule was expressed by comparing it with that of beta-actin mRNA. The AMI and UAP patients showed high frequencies of mRNA for IL-1beta, IL-8, TGF-beta, and ICAM-1 together with strong intensities of expression, whereas SAP patients showed decreased mRNA expression for these molecules. Increased IL-6 mRNA expression was observed only in AMI samples. Specimens from RS patients revealed an accumulated expression of proinflammatory cytokines, except for IL-6, as well as of TGF-beta. The study suggests that variation in mRNA expression may reflect the pathophysiology of specific types of coronary artery disease, and remodeling following vascular injury.
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PMID:Expression of cytokine and adhesion molecule mRNA in atherectomy specimens from patients with coronary artery disease. 1047 71

Interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, and the secreted form of the IL-1 receptor antagonist (sIL-1RA) are involved in the inflammatory response to inhaled grain dust. Previously, we found considerable production of these cytokines in the lower respiratory tract of workers exposed by inhalation to aqueous extracts of corn dust extract. Alveolar macrophages (AM) have long been considered the cell type responsible for producing these cytokines, and only recently has it been realized that airway epithelial cells may also be involved in cytokine production. In order to determine whether airway epithelia are involved in the inflammatory response to inhaled corn dust extract and to compare the magnitude of response of bronchial epithelial cells (BE) and bronchoalveolar lavage (BAL) cells, we used the reverse transcriptase/polymerase chain reaction (RT/PCR) technique in a semiquantitative manner to evaluate the concentration of IL-1beta, IL-6, IL-8, TNF-alpha, and sIL-1RA. Alveolar cells were obtained by BAL, and BE were obtained by endobronchial brush biopsy from 15 grain handlers 6 h after experimental inhalation of saline or an aqueous corn dust extract. After inhalation of saline, BE expressed low but detectable levels of IL-6, IL-8, and IL-1beta (> 1 complementary DNA [cDNA] molecule/cell). After inhalation of corn dust extract, the expression of messenger RNA (mRNA) for IL-1beta and IL-8 in the BE were significantly increased, whereas no change was seen in IL-6, sIL-1RA, and TNF-alpha mRNA expression. Comparing cytokine mRNA levels in BE and BAL cells from the same subjects after inhalation of corn dust extract, BE and BAL cells expressed equivalent amounts of IL-8 mRNA; IL-1beta was 11-fold higher in BAL cells; and TNF-alpha and sIL-1RA were expressed exclusively by BAL cells. Immunostaining for the cytokines in BAL cells showed cytokine protein expression in AMs but not in polymorphonuclear cells (PMNs). On the other hand, sIL-1RA was strongly expressed in both AMs and PMNs. Analysis of cytokine protein levels in endobronchial lavage (EBL) fluid demonstrated that only IL-8 was released in detectable amounts into the airway lumen, whereas all the other cytokines of interest were exclusively found in the BAL fluid. Thus, within 6 h after inhalation exposure to corn dust extract, BE appear to contribute to airway inflammation by producing IL-8. AMs are responsible for most of the IL-1beta and IL-6 production in the alveolar region, whereas AMs and PMNs both produce sIL-1RA. Our findings suggest that the inflammatory response to inhaled grain dust is compartmentalized, involving specific mediators of inflammation released by macrophages, neutrophils, and airway epithelial cells.
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PMID:Compartmentalization of the inflammatory response to inhaled grain dust. 1050 23

We present herein the case of a 48-year-old woman with a benign mediastinal teratoma that had been followed up for 3 years, who developed acute cardiac tamponade. The patient had initially undergone an exploratory sternotomy, at which time the tumor was histologically diagnosed as a benign mature teratoma that could not be resected due to its severe, wide adhesion to the surrounding organs. However, following the development of cardiac tamponade, both sternotomy and right intercostal thoracotomy were employed, and the tumor could be excised with cardiopulmonary bypass standby. High levels of amylase and carbohydrate antigen 19-9 were revealed in the pericardiac effusion fluid. The mRNA expression of inflammatory cytokines including interleukin-1 (IL-1), IL-6, and IL-8 in the tumor tissue was also demonstrated by a reverse transcriptase-polymerase chain reaction analysis. This case illustrates the ultimate natural course of benign mediastinal teratoma and emphasizes the importance of early surgical excision, even when this tumor is asymptomatic.
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PMID:Benign mediastinal teratoma complicated by cardiac tamponade: report of a case. 1055 43

Theophylline inhibits eosinophilic infiltration into the bronchial wall. It is unknown whether this is mediated by a cyclic adenosine monophosphate (c-AMP)-dependent reduction in eosinophil chemotactic activity (ECA) from bronchial epithelial cells (BEC). Therefore the effect of a beta2-agonist, procaterol and theophylline on the release of ECA from a BEC line, BEAS-2B was evaluated in response to interleukin (IL)-1beta and tumour necrosis factor-alpha (TNF-alpha). ECA was assessed using a blind-well chemotactic chamber, and the release and gene expression of cytokines were evaluated by means of enzyme-linked immunosorbent assay and reverse transcriptase polymerase chain reaction. IL-1beta and TNF-alpha stimulated the release of ECA from BEAS-2B cells in a dose- and time-dependent manner. Procaterol and theophylline directly inhibited eosinophil migration to IL-1beta and TNF-alpha-conditioned medium. The pretreatment of BEAS-2B cells with the same concentrations of procaterol inhibited the release of ECA in a dose-dependent fashion. Anti-IL-8, anti-regulated on activation, normal T-cell expressed and secreted (RANTES), and anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) inhibited ECA. Procaterol inhibited the release of RANTES, GM-CSF and IL-8 in a dose-dependent fashion. The effect of theophylline was less potent. Procaterol augmented cAMP levels in BEAS-2B cells in a time- and dose-dependent manner. The expression of IL-8, RANTES, and GM-CSF messenger ribonucleic acid was not inhibited by procaterol and theophylline. These data indicate that procaterol and theophylline may directly inhibit eosinophil migration and that procaterol may further inhibit the release of eosinophil chemotactic activity from BEAS-2B cells via a cyclic adenosine monophosphate-dependent mechanism. This warrants further studies on the involvement of bronchial epithelial cells in the anti-inflammatory effects of procaterol and theophylline in patients with asthma.
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PMID:Procaterol inhibits IL-1beta- and TNF-alpha-mediated epithelial cell eosinophil chemotactic activity. 1057 18

In patients with cystic fibrosis (CF), the progression of pulmonary disease differs considerably, even in identical cystic fibrosis transmembrane conductance regulator-genotypes which could reflect an additional influence of the host's immune response. This study therefore measured cytokine expression patterns in CF patients with different clinical presentation. Expression of interleukin (IL)-8, interferon gamma (IFN-gamma), IL-4, IL-10, and transforming growth factor (TGF)beta(I) was assessed in bronchial mucosal biopsies of eight CF patients with acute exacerbation (age 6.0-14.2 yrs), eight CF patients with chronic stable disease (age 7.3-17.4 yrs), and in five normal control subjects by semiquantitative and quantitative reverse transcriptase polymerase chain reaction combined with histopathological assessment and immunohistochemical staining. All CF patients expressed IL-8. In acute exacerbation, expression of TGF-beta1 and IFN-gamma was either absent or extremely low. In contrast, all patients with stable disease strongly expressed TGF-beta1. The highest expression of TGF-beta1 and IFN-gamma was found in CF patients with mild disease and a history of infrequent exacerbations. No correlation was found between the expression of IL-4 and IL-10 and patient history. In normal control subjects, only a weak expression of TGF-beta1 was observed. These results show a remarkable correlation between cytokine pattern and the clinical course of cystic fibrosis. High expression of transforming growth factor-beta1 and interferon gamma was associated with mild disease, whereas no or very weak expression of these cytokines was typical for patients with acute disease and frequent exacerbations suggesting a contribution of the immune response to the progression of pulmonary disease in cystic fibrosis.
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PMID:Cytokine expression in bronchial biopsies of cystic fibrosis patients with and without acute exacerbation. 1059 3


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