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

---

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

We investigated the kinetics of multiple cytokines and inducible nitric oxide synthase (iNOS) in experimental uveitis induced by bovine melanin protein (BMP) for the proper treatment of uveitis. Experimental uveitis was induced in male Lewis rats by injection of BMP. The levels of various inflammatory cytokines and iNOS mRNAs were semiquantified by the reverse-transcriptase reaction followed by PCR. The uveitis was started to develop at approximately day 14 and peaked around 21 days after immunization. The signs of uveitis disappeared by 4 weeks after immunization. When the inflammation was severest, TNF-alpha, IL-1alpha, IL-10, IFN-gamma and iNOS mRNA increased to their peak, which varied with the degree of induction and different time course. We concluded that both cytokines and iNOS might modulate the inflammation at different states of experimental melanin-protein-induced uveitis. Their combination will be necessary for an effective treatment of inflammation.
...
PMID:The expression of multiple cytokines and inducible nitric oxide synthase in experimental melanin-protein-induced uveitis. 1172 Nov 85

Caspase-associated recruitment domains (CARD) are protein-protein interaction modules found extensively in proteins that play important roles in apoptosis, NFkappaB activation, and cytokine regulation. In this study we identified a novel human protein, CARD-8, which contains a C-terminal CARD domain with high similarity to the CARD domain of caspase-1/ICE. We demonstrate that CARD-8 interacts physically with caspase-1 and negatively regulates caspase-1-dependent IL-1beta generation in the THP-1 monocytic cell line. CARD-8 binds also to ICEBERG and pseudo-ICE, two other recently identified proteins, which bind to the CARD domain of caspase-1 and negatively regulate its activity. Reverse transcriptase-PCR analysis revealed that CARD-8 is expressed mainly in monocytes, placenta, lymph nodes, and spleen. This pattern of expression is consistent with caspase-1 expression in the same cells and tissues. CARD-8 was also found to negatively regulate NF-kappaB activation by TNF-alpha stimulation and by ectopically expressed RICK, suggesting that this protein may control cell survival. Consistent with these results, stable expression of CARD-8 in U937 or THP-1 cells sensitizes the cells to differentiation-induced apoptosis. Overexpression of CARD-8 can also induce apoptosis in transfected cells. The results suggest that CARD-8 represents a new signaling molecule involved in the regulation of caspase-1 and NF-kappaB activation.
...
PMID:CARD-8 protein, a new CARD family member that regulates caspase-1 activation and apoptosis. 1182 83

Current knowledge implicates pleural mesothelial cells as mainly responsible for inflammatory responses in the pleural space. However, a vast body of recent evidence underscores the important role of fibroblasts in the process of inflammation in several types of tissues. We hypothesize that HPFBs (human pleural fibroblasts) play an important role in pleural responses and also when activated by bacterial endotoxin LPS (lipopolysaccharide), IL-1 beta (interleukin-1 beta), or TNF-alpha (tumor necrosis factor-alpha) release of C-C and C-X-C chemokines-specifically, MCP-1 and IL-8. Our results show that pleural fluid-isolated human fibroblasts release IL-8 and MCP-1 upon stimulation with IL-1 beta, TNF-alpha, and LPS in both a concentration- and time-dependent manner. RT-PCR (reverse-transcriptase-polymerase chain reaction) studies have also confirmed IL-8- and MCP-1-specific mRNA expression in activated pleural fibroblasts. On the time-dependent response curve, IL-8 was found in maximum concentrations at 144 hr, whereas MCP-1 continued to increase even after 196 hr following stimulation. IL-1 beta induced the maximum release of IL-8 (800-fold) and MCP-1 (164-fold), as compared to the controls. TNF-alpha induced a 95-fold increase in IL-8 and an 84-fold increase in MCP-1 levels, as compared to the controls. Collectively, our results show that human pleural fibroblasts contribute to the inflammatory cascade in the pleural space.
...
PMID:Inflammatory cytokines mediate C-C (monocyte chemotactic protein 1) and C-X-C (interleukin 8) chemokine expression in human pleural fibroblasts. 1198 90

Both innate and adaptive immune systems are thought to participate in the pathogenesis of rheumatoid arthritis in adults and children. The experiments reported here were undertaken to examine how immune complexes, potent stimulators of inflammation, may regulate cells of the adaptive immune system. Human T cells were prepared from peripheral blood by negative selection and incubated with bovine serum albumin (BSA)-anti-BSA immune complexes that were formed in the presence or absence of human C1q. C1q-bearing immune complexes, but not unopsonized complexes, elicited both TNF-alpha and IFN-gamma secretion from human T cells. Secretion of both cytokines was time- and dose-dependent. Cross-linking C1q on the cell surface of T cells produced the same results. Cytokine secretion was not inhibited by blocking the C3b receptor (CR1, CD35) on T cells prior to incubation with immune complexes. Reverse transcriptase polymerase chain reaction (RT-PCR) of immune complex-stimulated cells revealed accumulation of both TNF-alpha and IFN-gamma mRNA within 2 h post-stimulation. IL-2 was not detected in cell culture supernatants, but IL-2 receptor alpha chain (CD25) was detected in low density on a small proportion of T cells activated by C1q-bearing immune complexes. Secretion of both cytokines was inhibited partially, but not completely, by IL-10. These experiments show that immune complexes, potent inflammatory mediators, may activate T cells through a novel mechanism. These findings have implications for chronic inflammatory diseases in humans.
...
PMID:T cell activation by soluble C1q-bearing immune complexes: implications for the pathogenesis of rheumatoid arthritis. 1251 87

KE-758, an active metabolite of KE-298, is a novel sulfhydryl antirheumatic drug. We analyzed the effect of KE-758 on tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta production by a human monocytes cell line (THP-1 cells), stimulated with interferon-gamma (IFN-gamma) plus lipopolysaccharide (LPS). We compared the effects with other thiol-modifying antirheumatic drugs such as D-penicillamine, bucillamine and auranofin. THP-1 cells were treated with IFN-gamma for 16 h and were then exposed to LPS for an additional 6 h (for TNF-alpha detection) or 24 h (for IL-1 beta detection). The amounts of TNF-alpha and IL-1 beta in culture supernatants were measured using enzyme-linked immunosorbent assay. KE-758 and auranofin but not D-penicillamine and bucillamine significantly suppressed both TNF-alpha and IL-1 beta. Auranofin suppressed IL-1 beta production by reducing cellular viability. Reverse transcriptase-polymerase chain reaction analysis revealed that the suppressive effect of KE-758 is based on the inhibition of messenger ribonucleic acid expression of TNF-alpha and IL-1 beta. KE-758 had no effect on p75 and p55 soluble TNF receptor production in IFN-gamma and LPS-stimulated THP-1 cells. Thus, KE-758 inhibits both TNF-alpha and IL-1 beta production and its antirheumatic profile is apparently distinct from that of D-penicillamine, bucillamine and auranofin.
...
PMID:KE-758, an active metabolite of the new anti-rheumatic drug KE-298, suppresses production of tumor necrosis factor-alpha and interleukin-1 beta in THP-1, a human monocyte cell line. 1263 95

The activation of the transcription factor NF-kappaB is central to the control of the cellular response triggered by many stimuli. Once released from the inhibitory molecule IkappaB, NF-kappaB is translocated to the nucleus, and it has to be phosphorylated to activate transcription. In zeta protein kinase C (PKC)-deficient cells, NF-kappaB is transcriptionally inactive and the phosphorylation of the RelA subunit in response to tumor necrosis factor (TNF-alpha) is severely impaired. In vitro assays showed that zetaPKC directly phosphorylates RelA. Here we demonstrate that Ser311 accounts for zetaPKC phosphorylation of RelA and that this site is phosphorylated in vivo in response to TNF-alpha. Also, an inactivating mutation of that residue severely impairs RelA transcriptional activity, blocks its anti-apoptotic function and abrogates the interaction of RelA with the co-activator CBP as well as its recruitment, and that of RNA polymerase II (Pol II) with the interleukin-6 (IL-6) promoter. The interaction of endogenous CBP with endogenous RelA is inhibited in zetaPKC-/- cells, as well as the binding of Pol II to the IL-6 promoter. These results demonstrate the mechanism whereby zetaPKC regulates NF-kappaB activation in vivo.
...
PMID:Essential role of RelA Ser311 phosphorylation by zetaPKC in NF-kappaB transcriptional activation. 1288 25

The expression of the cytochrome P450 1A1 gene (cyp1a1) is regulated by the aryl hydrocarbon receptor (AhR), which is a ligand-activated transcription factor that mediates most toxic responses induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In the nucleus, ligand-activated AhR binds to the xenobiotic response elements, initiating chromatin remodeling and recruitment of coregulators, leading to the formation of preinitiation complex followed by elongation. Here, we report that ligand-activated AhR recruits the positive transcription elongation factor (P-TEFb) and RNA polymerase II (RNA PII) to the cyp1a1 promoter with concomitant phosphorylation of the RNA PII carboxyl domain (CTD). Interestingly, the serine 2 and serine 5 of the heptapeptide repeats (YSPTSPS) were sequentially phosphorylated upon TCDD treatment. Inhibition of P-TEFb kinase activity by 5,6-dichloro-1-beta-d-ribofuranosyl-benzimidazole (DRB) suppressed CTD phosphorylation (especially serine 2 phosphorylation) and abolished processive elongation without disrupting the assembly of the preinitiation complex at the cyp1a1 promoter. Remarkably, we found that activation of NF-kappaB by TNF-alpha selectively inhibited TCDD-induced serine 2 phosphorylation in mouse liver cells, suggesting that residue-specific phosphorylation of RNA PII CTD at the cyp1a1 promoter is an important regulatory point upon which signal "cross-talk" converges. Finally, we show that ligand-activated AhR associated with P-TEFb through the C terminus of cyclin T1, suggesting that AhR recruit the P-TEFb to the cyp1a1 promoter whereupon its kinase subunit phosphorylates the RNA PII CTD.
...
PMID:Interactions between the aryl hydrocarbon receptor and P-TEFb. Sequential recruitment of transcription factors and differential phosphorylation of C-terminal domain of RNA polymerase II at cyp1a1 promoter. 1291 20

To determine the role of NF-kappa B in ischemia reperfusion (I/R) injury of the rat liver, rats underwent partial hepatic ischemia and reperfusion. The left and median lobes of the liver were subjected to ischemia for 90 min followed by reperfusion for defined times. NF-kappa B activity was analyzed by electrophoretic mobility shift assay (EMSA). Semiquantitative reverse-transcriptase polymerase chain reaction was used to analyze TNF-alpha and ICAM-1 mRNA levels. Results showed during liver I/R injury, NF-kappa B activation was induced in a time dependent manner. NF-kappa B was activated within 1 h and 2 h after the initiation of reperfusion and decreased after 4 h. Messenger RNA expression of TNF-alpha and ICAM-1 were increased after the reperfusion of 2 h. It was concluded that during hepatic I/R injury, NF-kappa B was activated and could bind to special sequence in the promoters of budget genes, which can up-regulate the expression of TNF-alpha and ICAM-1 mRNA to result in ischemia reperfusion injury of the rat liver.
...
PMID:Role of NF-kappa B in liver ischemia reperfusion injury of rats. 1297 36

Hyaluronan (HA) is an important constituent of the extracellular matrix and accumulates during inflammatory lung diseases like asthma. Little is known about the factors that regulate HA synthesis by lung cells. Accordingly, we investigated the effect of T-helper 1 (TH1) and 2 (TH2) cytokines and the anti-inflammatory agents fluticasone and salmeterol on HA synthesis in human lung fibroblasts. Interleukin-1beta (IL-1beta) and tumor necrosis factor (TNF)-alpha were the most potent stimulators of HA synthesis and when combined, caused synergistic increases in HA accumulation. Time-course analysis of HA accumulation and [3H]-glucosamine incorporation into HA demonstrated continued synthesis over the 24 h of stimulation. Peak synthesis at 6-12 h coincided with an increased proportion of high molecular weight HA. Reverse transcriptase polymerase chain reaction (RT-PCR) revealed that IL-1beta and TNF-alpha induced HA synthase-2 messenger RNA (mRNA) 3 h following stimulation and remained elevated throughout the 24-h stimulation period. Fluticasone inhibited IL-1beta and TNF-alpha induced HA synthesis (44.5%) whereas salmeterol had no effect. When combined, fluticasone and salmeterol inhibited HA synthesis to a greater extent (85.2%). Further, fluticasone attenuated IL-1beta and TNF-alpha stimulated hyaluronan synthase-2 messenger RNA (mRNA), and the addition of salmeterol cooperatively enhanced this inhibition. These results indicate that enhanced synthesis of HA by the proinflammatory cytokines IL-1beta and TNF-alpha can be abrogated by specific corticosteroid and beta2 blocker combinations shown to be effective in the treatment of asthma.
...
PMID:Pro- and anti-inflammatory factors cooperate to control hyaluronan synthesis in lung fibroblasts. 1476 29

Angiotensin (Ang) II is now recognized to be a mediator of a wide variety of inflammatory processes. This study investigated renin-angiotensin system (RAS) components and a number of inflammatory mediators in left ventricular biopsies from 2-vessel disease unstable angina (UA) (n=43) and stable angina (SA) (n=15) patients undergoing coronary bypass surgery. Biopsy samples from 6 patients undergoing valve replacement for mitral stenosis served as controls. UA patients were randomly assigned to angiotensin-converting enzyme (ACE)-inhibitor (ramipril), AT1 antagonist (valsartan), or placebo and treated during the 5 days preceding coronary bypass surgery, performed from 6 to 9 days after coronary angiography. During coronary angiography coronary blood flow was measured and samples were obtained from aorta and coronary sinus for determination of Ang I and Ang II gradients. The hearts of UA patients produced Ang II in a greater amount than in SA patients (P<0.01). UA biopsy samples showed numerous DR+ cells, identified as lymphocytes, macrophages, and endothelial cells. Reverse-transcriptase polymerase chain reaction showed overexpression of AGTN, ACE, and AT1-R genes, as well as upregulation of TNF-alpha, IL-6, IFN-gamma, and iNOS genes (P<0.01), with no differences between nonischemic and potentially ischemic areas. AGTN, ACE, and cytokine genes were mainly localized on endothelial cells. Ramipril and valsartan markedly decreased the expression levels of TNF-alpha, IL-6, and iNOS, and, to a lesser extent, of IFN-gamma genes, but did not affect the number of DR+ cells, with no significant difference between the 2 treatments. These results show that locally generated Ang II amplifies the immunomediated inflammatory process of coronary microvessels occurring in unstable angina.
...
PMID:Cardiac angiotensin II participates in coronary microvessel inflammation of unstable angina and strengthens the immunomediated component. 1521 17


<< Previous 1 2 3 4 5 6 7 8 Next >>

---