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)

Production and release of proinflammatory mediators such as tumour necrosis factor-alpha and neopterin are common events following the activation of the cellular immune system. Concerning inflammatory disorders of the lung, e.g. sepsis or sarcoidosis, high serum neopterin levels have been reported to correlate well with the severity of the disease. These situations are often associated with an increased expression of ICAM-1 reported to be induced in type II alveolar epithelial cells. In our study we investigated the potential effects of neopterin on ICAM-1 synthesis in the type II-like pneumocyte cell line L2. Detection of ICAM-1 gene expression by reverse transcriptase-polymerase chain reaction revealed a dose-dependent effect of neopterin, with maximum impact following 12-h incubations. Comparable results were obtained when ICAM-1 protein synthesis was measured via a cell-based ELISA. In a second set of experiments we were able to show that coincubation of L2 cells with pyrrolidine dithiocarbamate (PDTC) significantly suppressed neopterin-induced ICAM-1 synthesis. Since PDTC is known to be a potent inhibitor of NF-kappaB, the stimulating effects of neopterin on ICAM-1 gene expression and protein generation may be mediated by activation of this transcription factor. From these data we conclude that neopterin stimulates ICAM-1 production in L2 cells. In vivo, these effects may contribute to the prolongation of the inflammatory response, including cytotoxic cell host defence mechanisms that impair the functions of the airway epithelium.
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PMID:Neopterin-induced expression of intercellular adhesion molecule-1 (ICAM-1) in type II-like alveolar epithelial cells. 1059 64

Insulin-like growth factor-1 (IGF-1) is a highly mitogenic polypeptide detectable in human lung. Using competitive reverse transcriptase/polymerase chain reaction (RT-PCR), expression of four IGF-1 transcripts was examined in bronchoalveolar lavage cells (BALC) from normal subjects, idiopathic pulmonary fibrosis (IPF), stage I/II (no fibrosis), and stage III/IV (confirmed fibrosis) pulmonary sarcoidosis patients, and fibroblast strains isolated from normal and IPF lungs. Transcripts studied were Class 1 and Class 2 (exons 1 or 2, respectively) with IGF-1Eb or IGF-1Ea (exons 5 or 6, respectively). Total IGF-1 expression was downregulated in BALC of both patients with IPF (p < 0.01) and patients with sarcoidosis (p < 0.04) compared with healthy subjects. In contrast, both constitutive (p < 0.003) and transforming growth factor-beta (TGF-beta)- induced (p < 0.02) IGF-1 expression was higher in fibrotic, compared with normal, fibroblasts. These changes were associated with differential expression of IGF-1 splice variants. Healthy subjects and sarcoidosis patients without fibrosis showed similar expression of Class 1/Class 2 and IGF-1Ea/IGF-1Eb. However, patients with fibrosis demonstrated discordant, increased relative abundance of Class 1 transcripts (p < 0.01). In parallel, all fibrosis patients failed to express Class 2, IGF-1Eb forms and sarcoidosis patients with fibrosis did not express the Class 1, IGF-1Eb variant either. Fibrotic fibroblasts expressed higher constitutive levels of Class 1, IGF-1Ea transcripts compared with normal fibroblasts. Class 2, IGF-1Eb forms were moderately expressed by fibroblasts only after stimulation with TGF-beta, which also further increased levels of Class 1, IGF-1Ea transcripts. Our findings suggest that transition from a healthy to a fibrotic phenotype occurs in association with a changing pattern of IGF-1 mRNA heterogeneity and leads us to hypothesize a potential role for specific IGF-1 variants in fibrogenesis.
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PMID:Differential mRNA expression of insulin-like growth factor-1 splice variants in patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis. 1146 99

The chemokines RANTES (regulated on activation, T-cell expressed and secreted; CC chemokine ligand (CCL)-5) and monocyte inflammatory protein (MIP)-1alpha (CCL-3) have been implicated in the development of alveolitis in pulmonary sarcoidosis. The novel C chemokine single cysteine motif (SCM)-1alpha (XCL-1) and the CC chemokine monocyte chemoattractant protein (MCP)-1 (CCL-2) are also mononuclear-cell attractants and represent alternative candidate mediators of alveolitis. Therefore, the expression of MCP-1 and SCM-1alpha was investigated together with the expression of RANTES and MIP-1alpha in bronchoalveolar lavage fluid (BALF) from control subjects and patients with sarcoidosis. The relationship between chemokine expression and sarcoidosis clinical course was also explored. Messenger ribonucleic acid (mRNA) expression for all four chemokines was determined by semiquantitative reverse transcriptase-polymerase chain reaction of RNA extracted from unseparated bronchoalveolar cells (17 patients, 12 controls). RANTES, MIP-1alpha and MCP-1 proteins were measured by enzyme-linked immunosorbent assay of unconcentrated BALF (60 patients, 17 controls). MCP-1, and namely RANTES and SCM-1alpha mRNA expression was upregulated in sarcoidosis, particularly in patients with more advanced disease. RANTES, and namely MCP-1 concentrations were elevated in BALF samples obtained from patients; MCP-1 levels were most increased in patients with chest radiographic stage 2 disease and also in patients with persistent and recurrent disease. In conclusion, chemokines monocyte chemotactive protein-1 and single cysteine motif-1alpha are, in addition to RANTES, associated with the development of alveolitis in sarcoidosis and their expression parallels the disease course.
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PMID:CC and C chemokine expression in pulmonary sarcoidosis. 1244 75

In sarcoid granulomas, apoptotic events are reduced, which explains their characteristic long-lasting inflammation. We have described that interferon-gamma (IFN-gamma) inhibits apoptosis in macrophages through the expression of p21(Waf1). Here, we explore the molecular mechanisms involved in the inhibition of apoptosis in sarcoid granulomas. We analyzed skin biopsies from 19 sarcoidosis patients and 16 controls. Total RNA was subjected to semiquantitative reverse transcriptase-polymerase chain reaction analysis. There was no difference found in the expression of proapoptotic (Bax and Bcl-X(s)) or antiapoptotic (Bcl-2 and Bcl-X(L)) genes nor in the expression of the tumor suppressor gene p53. Furthermore, the expression of IFN-gamma and the cdk inhibitors p21(Waf1) and p27(Kip1) were analyzed. IFN-gamma was detected in 37% of the sarcoidosis patients, and controls were negative (P<0.02). In addition, a higher proportion of patients expressing p21(Waf1) (58%) versus controls (12%) was found (P<0.005). There was a significant correlation between the expression of IFN-gamma and p21(Waf1) (r=0.69) and between p21(Waf1) and fibronectin (r=0.65). Finally, using immunohistochemistry, high p21(Waf1) reactivity was observed inside the granuloma. We conclude that the high levels of p21(Waf1) in sarcoidosis may explain the absence of apoptosis in the granuloma and the persistence of inflammation.
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PMID:High expression of p21 Waf1 in sarcoid granulomas: a putative role for long-lasting inflammation. 1288 47

Substance P (SP) is a proinflammatory neuropeptide that is secreted by sensory nerves and inflammatory cells. Increased levels of SP are found in sarcoid bronchoalveolar lavage fluid. SP acts by binding to the neurokinin-1 receptor and increases secretion of tumor necrosis factor-alpha in many cell types. We sought to determine neurokinin-1 receptor expression in patients with sarcoidosis compared with normal controls. Neurokinin-1 receptor messenger RNA and protein expression were below the limits of detection by reverse transcriptase-polymerase chain reaction and immunohistochemistry in peripheral blood mononuclear cells of healthy volunteers (n = 9) or patients with stage 1 or 2 pulmonary sarcoidosis (n = 10), but were detected in 1/9 bronchoalveolar lavage cells of controls compared with 8/10 patients with sarcoidosis (p = 0.012) and 2/9 biopsies of controls compared with 9/10 patients with sarcoidosis (p = 0.013). Immunohistochemistry localized upregulated neurokinin-1 receptor expression to bronchial and alveolar epithelial cells, macrophages, lymphocytes, and sarcoid granulomas. The patient in whom neurokinin-1 receptor was not detected was taking corticosteroids. Incubation of the type II alveolar and bronchial epithelial cell lines A549 and SK-LU 1 with dexamethasone downregulated neurokinin-1 receptor expression. Upregulated neurokinin-1 receptor expression in patients with sarcoidosis may potentiate substance P-induced proinflammatory cytokine production in patients with sarcoidosis.
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PMID:Upregulation of neurokinin-1 receptor expression in the lungs of patients with sarcoidosis. 1460 51

A single nucleotide polymorphism (SNP) C5507G of the complement receptor 1 (CR1) gene has been associated with genetic susceptibility to sarcoidosis in an Italian population. In order to provide further data on the possible involvement of CR1 gene polymorphisms in sarcoidosis, CR1 SNPs C5507G and A3650G were investigated in Czech (n = 210) and Dutch (n = 116) patients with sarcoidosis with ethnically matched groups of healthy control subjects (Czech, n = 203; Dutch, n = 112). CR1 C5507G and A3650G SNPs were not associated with susceptibility to sarcoidosis or its clinical course. Further, CR1 messenger RNA expression in bronchoalveolar lavage cells investigated by quantitative reverse transcriptase-polymerase chain reaction did not differ between sarcoidosis patients and control subjects and was not associated with the presence of the CR1 5507*G allele.
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PMID:Complement receptor 1 single nucleotide polymorphisms in Czech and Dutch patients with sarcoidosis. 1799 56


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