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:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Detection of rejection after small intestine transplantation (SIT) is difficult, relying largely on histopathology. The purpose of this study was to determine if the intragraft expression of messenger RNA (mRNA) for interleukin-2 receptor (IL-2R), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF) correlated with rejection in a unidirectional, heterotopic rat SIT model. Graft samples were obtained on postoperative day (POD) 3, 5, 7, 8, 9, 10, 12, and 14. After staining, formalin-fixed samples were blindly evaluated for rejection. Reverse transcriptase polymerase chain reaction (rtPCR) using primers specific for beta-actin, IL-2R, IL-6, and TNF was performed on liquid nitrogen-frozen samples. Semiquantitation was accomplished using radionuclide incorporation and beta-scintillation counting. Intestinal histopathology in all isografts (ISO) and POD 3 allografts (ALLO) was normal. Rejection progressed in ALLO from mild on POD 5 to severe by POD 8. rtPCR analysis revealed constitutive expression of IL-2R mRNA in both ISO and ALLO. TNF and IL-6 demonstrated significant increases in mRNA expression in ALLO compared to ISO beginning on POD 5. In summary, intragraft expression of IL-2R mRNA demonstrated late up-regulation in ALLO which did not correlate with rejection. TNF and IL-6 mRNA expression predicted rat SIT rejection. rtPCR analysis of TNF and IL-6 may serve as a useful diagnostic adjunct for rat SIT rejection.
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PMID:Intragraft expression of messenger RNA for interleukin-6 and tumor necrosis factor-alpha is a predictor of rat small intestine transplant rejection. 804 Nov 28

Proteins that have been modified by long-term expose to glucose accumulate advanced glycosylation end products (AGEs) as a function of protein age. In these studies, we have examined the interaction of AGE-protein with renal cell carcinoma cells (RCC) in vitro, using AGE-modified bovine serum albumin (AGE-BSA) as a probe. AGE-BSA showed tendency to induce in vitro cell growth of RCC cells and promoted the production of interleukin-6 (IL-6), an in vitro autocrine growth factor. Reverse transcriptase-polymerase chain reaction analysis revealed that RCC cells used here express mRNA for a receptor for AGEs (RAGE). These results suggested that AGEs taken up through RAGE on RCC cells might play a role in promoting the growth of RCC cells.
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PMID:Expression of receptors for advanced glycosylation end products on renal cell carcinoma cells in vitro. 824 Mar 77

Two cases of mycosis fungoides (MF) in the tumor stage were treated with intra-lesional interferon-gamma (IFN-gamma) therapy. After systemic chemotherapy, intra-lesional recombinant interferon-gamma was applied to the residual tumors. Intra-lesional IFN-gamma was sufficiently effective in the treatment of MF tumors, especially small-sized ones. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis of messenger RNA expression of cytokines commonly detected interleukin-6 (IL-6) and IFN-gamma in the tumor cells before intra-lesional IFN-gamma. However, in our study, tumor cells in these cases did not exhibit the definitive cytokine patterns of Th1 or Th2.
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PMID:Cytokine profile of tumor cells in mycosis fungoides: successful treatment with intra-lesional interferon-gamma combined with chemotherapy. 853 50

The oral commensal Gram-negative bacterium Actinobacillus actinomycetemcomitans is believed to be the causative organism of localized juvenile periodontitis, a disease in which there is rapid loss of alveolar bone supporting the teeth. Previously, we have reported that gentle saline extraction of this bacterium removed a loosely adherent proteinaceous fraction from the cell surface of the bacterium, which we have termed surface-associated material. This material contained potent bone-resorbing activity. We now report that surface-associated material is also a potent stimulator of cytokines, and in particular, interleukin-6 (IL-6) synthesis, while the lipopolysaccharide from this bacterium is only a weak stimulator of IL-6 synthesis by fibroblasts and monocytes. In contrast to enteric lipopolysaccharide (LPS), which induces fibroblast IL-1, IL-6 and tumour necrosis factor (TNF) alpha synthesis, surface-associated material stimulated gingival fibroblasts to synthesize only IL-6, with no induction of IL-1 or TNF (the normal inducers of IL-6 synthesis). Reverse transcriptase PCR also failed to detect mRNA for IL-1 or TNF in surface-associated-material-stimulated fibroblasts, although both mRNAs were present in Escherichia coli LPS-stimulated cells. Neutralizing antibodies to IL-1 and/or TNF or the natural IL-1 receptor antagonist (IL-1ra) inhibited enteric LPS-induced IL-6 synthesis, but did not inhibit surface-associated-material-induced synthesis. In addition, dexamethasone, which completely suppressed LPS-induced IL-6 synthesis, only inhibited surface-associated-material-induced IL-6 synthesis by 50%. This suggests that the active constituent in the surface-associated material stimulates IL-6 gene transcription by a transcriptional control mechanism distinct to that of E. coli LPS. The IL-6 stimulating activity of the surface-associated material is inhibited by both heat and trypsin, suggesting that it is proteinaceous. The activity has been isolated using anion-exchange, reverse-phase and size-exclusion HPLC. The active moiety is a peptide of molecular mass 2kDa which may be the product of a bacterial short open reading frame.
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PMID:Surface-associated material from the bacterium Actinobacillus actinomycetemcomitans contains a peptide which, in contrast to lipopolysaccharide, directly stimulates fibroblast interleukin-6 gene transcription. 866 8

Here we review our recent experience addressing the role of SCF in multiple myeloma (MM). We first investigated the proliferation of MM cell lines and bone marrow samples from myeloma patients in response to rh-SCF alone and combined with Interleukin-6 (IL-6), IL-3, and IL-3/GM-CSF fusion protein PIXY 321. Neoplastic plasma cells were highly purified (>90%) by immunomagnetic depletion of T, myeloid, monocytoid and NK cells. The number of S-phase cells was evaluated after 3 days of liquid culture by the bromodeoxyuridine (BRDU) incorporation assay. The proliferation of RPMI 8226 and U266 cell lines was also assessed by a clonogenic assay. All the experiments were performed in serum-free conditions. RPMI 8226 cell line was not stimulated by SCF which also did not augment the proliferative activity of IL-6, IL-3 and PIXY-321. Conversely, SCF addition resulted in 2.4-fold increase of the number of U266 colonies and in a higher number of U266 and MT3 cells in S-phase. The c-kit ligand also enhanced the proliferation of MT3 and U266 cells mediated by the other cytokines. Anti-SCF polyclonal antibodies completely abrogated the proliferative response of MT3 cells to exogenous SCF and markedly reduced the spontaneous growth of the same cell line. Reverse transcriptase-polymerase chain reaction amplification (RT-PCR) did detect SCF mRNA in MT3 and RPMI 8226 cells. Moreover, secreted SCF was found, in a biologically active form, in the supernatant of the two cell lines by the MO7e proliferation assay. These results suggest that an autocrine proliferative loop may be operative in MT3 cell line. When tested on fresh myeloma samples, SCF increased the number of S-phase plasma cells (4.7 +/- 1.6% vs 3.4 +/- 1.3% in control cultures; p = 0.02). Significant proliferation was also induced by IL6, IL-3 and PIXY-321. The addition of SCF significantly enhanced the proliferation of myeloma cells responsive to IL-6. Preliminary experiments performed on circulating plasma cells and myeloma precursors further supported the role of SCF on the proliferation of the neoplastic clone in MM.
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PMID:C-kit ligand (SCF) in human multiple myeloma cells. 883 3

The ancient drug colchicine has repeatedly been proposed as a novel drug for therapy of pulmonary fibrosis. The present study was undertaken to add to the knowledge on colchicine's antiinflammatory and antifibrotic properties and thus help determine its actual rank in the treatment of pulmonary fibrosis. In vitro cell culture experiments with stimulated and unstimulated normal donor peripheral blood mononuclear cells (PMNC) and a human lung fibroblast cell line (WI-38) were used to determine the effects of colchicine on PMNC cytokine release (interleukin-6 and tumor necrosis factor-alpha) as well as on fibroblast proliferation and collagen synthesis rates. Reverse transcriptase polymerase chain amplifications of alpha 1 (III) collagen were done to detect collagen messenger ribonucleic acid (mRNA) expression. Colchicine did not significantly modulate tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) release of PMNC. Colchicine inhibited fibroblast proliferation and total collagen synthesis significantly at concentrations obtainable in serum in vivo. Transcription of the alpha 1 (III) collagen gene into mRNA continued under colchicine. We conclude that colchicine is a potent in vitro inhibitor of fibroblast functions in terms of proliferation and collagen synthesis. The mechanism of collagen inhibition is more likely an inhibition of cellular collagen secretion than a switch off of collagen mRNA transcription. On the other hand, although colchicine is known to inhibit many leukocyte functions, it is a poor inhibitor of cytokines known to be important for fibrogenesis (e.g. IL-6, TNF-alpha, IL-1, platelet-derived growth factor, and transforming growth factor-beta). This makes colchicine, at least from a theoretical standpoint and as concluded from in vitro studies, a preferable candidate for a combined therapeutic strategy.
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PMID:Antiinflammatory and antifibrotic properties of colchicine: implications for idiopathic pulmonary fibrosis. 895 72

Although the liver is the primary site of fibrinogen (FBG) synthesis, epithelial cells from diverse tissues have been shown to express one or more of the FBG A alpha, B beta, and gamma chain genes. In contrast, marrow megakaryocytes, which store FBG in the alpha-granules, are thought not to express the FBG genes. Our earlier studies have shown that epithelial cells in a variety of extrahepatic tissues express the gamma chain gene ubiquitously, while the mRNAs for the A alpha and B beta chain genes are essentially undetectable. During systemic inflammation, the liver secretes increased levels of FBG into the circulation, and lung epithelium responds to local inflammation during pulmonary infection by increased transcription of the gamma-FBG gene. Therefore, to determine whether extrahepatic epithelial cells express the A alpha, B beta, and gamma chain genes in response to proinflammatory mediators, cultured lung epithelial cells were treated with interleukin-6 (IL-6) and dexamethasone (DEX). Northern blot analysis demonstrated that the levels of gamma-FBG mRNA in cultured lung (A549) and liver (HepG2) epithelial cells increased 2- to 10-fold in response to treatment. Reverse-transcriptase-polymerase chain reaction amplification demonstrated increased accumulation of steady state levels of FBG A alpha, B beta, and gamma chain mRNAs in lung epithelial cells after treatment. The basal level of lung cell gamma-FBG gene transcription was not accompanied by appreciable levels of A alpha and B beta chain gene transcription; however, nuclear run-on analysis suggested that the increase in lung cell FBG mRNAs in response to DEX +/- IL-6 was due to new transcription. Furthermore, stimulation of lung epithelial cells with IL-6 + DEX resulted in maximal secretion of intact FBG (340 kD) composed of the characteristic A alpha, B beta, and gamma chain polypeptides. The data suggest that basal expression of the gamma-FBG gene in extrahepatic tissue occurs ubiquitously in the absence of detectable levels of A alpha- and B beta-FBG gene expression, which are then upregulated on induction of an inflammatory response. This would result in local synthesis and secretion of FBG in the injured tissue, supporting the hypothesis that production of FBG by extrahepatic epithelial cells in response to inflammation plays a role in wound repair.
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PMID:Induction of fibrinogen biosynthesis and secretion from cultured pulmonary epithelial cells. 902 18

This study examines how interleukin-6 (IL-6) expression by human luteinizing granulosa cells is regulated. IL-6 was assayed in culture supernatants, mRNA in cells by in situ hybridization and by a competitive reverse-transcriptase polymerase chain reaction (RT-PCR). TNF alpha (100 pg-1 ng/ml) induced IL-6 mRNA and protein. Phorbol 12-myristate 13-acetate (PMA) (50 nM) mimicked this effect. DibutyrylcAMP (1 mM) and 10 microM forskolin. C2-, C6- and C8-ceramide (15 microM), all had no effect. The inhibitor of protein tyrosine kinase (PTK), genistein (100 micrograms/ml) reduced tumor necrosis factor (TNF) effects. The inhibitors of protein kinase C (PKC) (staurosporine, 10 nM), of phospholipase C (U73122, 2 microM), of phospholipase A2 (PLA2), (indomethacin 30 microM, mepacrin 50 microM, nordihydroguaiaretic acid 10 microM, ONO-RS-082 3,5 microM), none prevented it. Hence, IL-6 is induced by TNF alpha via activation of PTK. Protein kinase A, phosphoinositide and conventional PKC, sphingomyelin and PLA2 pathways are not implicated.
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PMID:Tumor necrosis factor-alpha induces interleukin-6 mRNA and protein in human granulosa luteinizing cells via protein tyrosine kinase without involving ceramide. 908 55

Endothelins (ET) are vasoactive polypeptide hormones that stimulate osteoblastic signal transduction events. Using MC3T3-E1 and primary osteoblasts, we studied ET effects on interleukin-6 (IL-6) and macrophage colony-stimulating factor (M-CSF) production. Enzyme-linked immunosorbent assay analysis showed a dose-dependent 3- to 3.5-fold increase in IL-6 with 100 nM ET-1 stimulation within 4 (primary osteoblasts) to 8 (MC3T3-E1) h. ET-3 was less effective at enhancing IL-6 production, with a maximal twofold increase after 100 nM ET-3 after 4 h. No significant increase in M-CSF production was noted with ET-1 or ET-3 in either cell type. Reverse-transcriptase polymerase chain reaction analysis demonstrated both ET(A) and ET(B) receptors on primary osteoblasts and only ET(A) receptors on MC3T3-E1. ET-1-stimulated IL-6 production was blocked by the inhibitor BQ-123, implicating ET(A) receptor involvement. Increased IL-6 protein was coupled with elevated IL-6 mRNA levels and a twofold increase in IL-6 message half-life.
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PMID:Endothelin stimulates osteoblastic production of IL-6 but not macrophage colony-stimulating factor. 912 53

Bronchial epithelial cells play an important role in the pathogenesis of some inflammatory diseases of bronchial mucosa. Epithelial-cell-derived cytokines are important in the elucidation of the mechanism by which airway inflammation occurs, especially in respiratory virus infection, because these cells are the primary sites of viral infection. We infected bronchial epithelial cells, NCI-H292, with influenza virus A (H3N2) and examined the concentrations of cytokines, interleukin-6 (IL-6), IL-8 and regulated on activation, normal T cells, expressed and secreted (RANTES), in the culture media of infected cells using the enzyme-linked immunosorbent assay system and gene expression of RANTES on epithelial cells by the reverse-transcriptase-polymerase chain reaction method. We found that significant amounts of IL-6, IL-8 and RANTES were released. RANTES mRNA was also detected in infected bronchial epithelial cells. It is suggested that cytokine production in human bronchial epithelial cells may contribute to the pathogenesis of airway inflammatory disorders.
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PMID:Expression of cytokines on human bronchial epithelial cells induced by influenza virus A. 913 May 60


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