Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclic GMP is the second messenger in the phototransduction mechanism in rod photoreceptors. Light-induced activation of cGMP phosphodiesterase (PDE), the hydrolyzing enzyme of cGMP, reduces cytoplasmic cGMP concentration to close the cGMP-activated channel and thereby causes a hyperpolarizing light response. Ca2+ concentration decreases during light-adaptation and this decrease is thought to be at least one of the underlying mechanisms of light-adaptation. Our previous electrophysiological work suggested that PDE in frog rod photoreceptors is regulated by this Ca2+ concentration decrease. In the present work, we isolated a protein that binds to disk membranes at high Ca2+ concentrations. In the presence of this protein (a 26 kDa protein), PDE light sensitivity becomes high at high Ca2+ concentrations. The effect was observed at physiological ranges of Ca2+ concentrations. Thus we could explain high light-sensitivity of photoreceptors under the dark-adapted condition. According to its function, we termed the 26 kDa protein 'sensitivity-modulating protein' or 'S-modulin'. During the purification we noticed that there are additional mechanisms present that may contribute to light-adaptation in frog rod photoreceptors.
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PMID:Light-sensitivity modulating protein in frog rods. 133 15

The expression in human fibroblasts of the beta 2-interferon (IFN-beta 2) gene, which is now recognized to be identical to the gene encoding B-cell differentiation factor BSF-2, is enhanced by several cytokines that affect cell growth (tumor necrosis factor, interleukin 1, platelet-derived growth factor, and beta 1-interferon). We have examined the possibility that IFN-beta 2 gene expression is regulated through activation, by diacylglycerol, of the protein kinase C pathway. The synthetic diacylglycerols 1,2-dioctanoylglycerol (diC8) and 1-oleoyl-2-acetylglycerol strongly enhanced IFN-beta 2, but not IFN-beta 1, gene expression in human fibroblasts (FS-4 strain). An increase in IFN-beta 2 mRNA level was detected within 15 min after addition of diC8 (290 microM) to FS-4 cells and was maximal approximately 20 hr later. An increase in IFN-beta 2 gene transcription was detected within 5 min of addition of diC8, and the rate of transcription was near-maximal by 15-30 min. The enhancement of IFN-beta 2 gene expression by diC8, interleukin 1, or tumor necrosis factor was not prevented by H8, a preferential inhibitor of cAMP- and cGMP-dependent protein kinases, but was blocked by H7, an inhibitor of protein kinase C as well as of cyclic nucleotide-dependent protein kinases. diC8 was found to protect FS-4 cells from the cytopathic effect of vesicular stomatitis virus; this protection was blocked by polyclonal or monoclonal antibodies that neutralize IFN-beta, suggesting that the antiviral effect was due to the secretion of IFN-beta 2 by the diC8-treated fibroblasts. The calcium ionophore A23187 (1-10 microM) also elicited an increase in the level of IFN-beta 2 mRNA in FS-4 fibroblasts; appropriate combinations of A23187 and diC8 had at least an additive effect in enhancing IFN-beta 2 mRNA levels. These results show that protein kinase C-activating or [Ca2+]-elevating agents rapidly increase the expression of the IFN-beta 2 gene in human fibroblasts.
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PMID:Rapid enhancement of beta 2-interferon/B-cell differentiation factor BSF-2 gene expression in human fibroblasts by diacylglycerols and the calcium ionophore A23187. 310 77

Cytokines have significant roles in some cardiovascular disorders, but direct myocardial effects of cytokines remain to be elucidated. In the present study, we examined both the early and delayed effects of interleukin-6 (IL-6) on cultured chick embryo ventricular myocytes. Exposure of these cells to human recombinant IL-6 significantly decreased peak systolic [Ca2+]i (71.0 +/- 0.6% of the control value) and the amplitude of cell contraction (66.0 +/- 7.4% of the control value) within a few minutes. Pretreatment with NG-monomethyl-L-arginine (L-NMMA) or methylene blue completely inhibited the IL-6-induced early changes. Subsequent addition of L-arginine reversed the effects of L-NMMA. The levels of cGMP were significantly increased after 30 minutes of exposure to IL-6 (134.4 +/- 9.1% of the control value). Pretreatment with L-NMMA or EGTA significantly inhibited the IL-6-induced early elevation of cGMP. These results suggest that IL-6 acutely decreases intracellular Ca2+ transients and depresses cell contraction by nitric oxide (NO)-cGMP-mediated pathway. Therefore, IL-6 may enhance the Ca(2+)-dependent constitutive NO synthase activity in cardiac myocytes. On the other hand, 24-hour exposure to IL-6 also increased the levels of cGMP (159.0 +/- 22.8% of the control value) regardless of pretreatment with EGTA. These delayed increases in cGMP were also shown to be coupled with decreases in intracellular Ca2+ transients and the amplitude of cell contraction. Thus, IL-6 may induce Ca(2+)-independent NO synthase in cardiac myocytes. Together with the previous reports that have suggested the possible roles of IL-6 in myocardial stunning or endotoxic shock, this negative inotropic effect of IL-6 may contribute to these clinical settings.
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PMID:Nitric oxide-mediated effects of interleukin-6 on [Ca2+]i and cell contraction in cultured chick ventricular myocytes. 751 62

In animal models authors have dealt with the question of whether hypotension alone can cause an acute-phase response even in the absence of marked blood loss and trauma. Sodium nitroprusside (SNP), which was employed in the animal models, is also used to induce hypotension in humans. Since no data are available on human subjects plasma concentrations of interleukin-6 (IL-6), an important mediator of the acute-phase response, were studied in patients during SNP infusion for induction of hypotension. METHODS. After approval by the local ethics committee, 20 patients scheduled for elective oto-rhino-laryngological operations participated in this randomised prospective study. Anaesthesia was induced with fentanyl, etomidate, vecuronium and succinylcholine and was maintained with isoflurane in 66% N2O and 33% O2. Ten patients received SNP to reduce mean arterial blood pressure to 50 mmHg, while another ten patients served as controls. Blood samples were taken before the induction of anaesthesia, during surgery (at the end of the SNP infusion), 60 min after surgery and on the day after surgery. IL-6 concentrations were determined by means of enzyme-linked immunosorbent assay. Epinephrine and norepinephrine in plasma were measured by high-pressure liquid chromatography with electrochemical detection. RESULTS. The IL-6 plasma concentration increased significantly from 3.2 (0-7.5) pg/ml (median and range) to 31.8 (9-42.2) pg/ml in the SNP group and from 3.5 (0-8.3) pg/ml to 15.2 (7.4-19) pg/ml in the control group on the morning after surgery. The IL-6 values at this time were significantly (P < 0.05) higher in the SNP group than in the controls. Norepinephrine increased significantly from 263 (150-920) pg/ml (median and range) preoperatively to 419 (115-897) pg/ml, and the epinephrine concentrations rose significantly from 77 (12-159) pg/ml to 115 (83-330) pg/ml at the end of SNP administration. No significant changes in the catecholamine concentrations were observed in the control group. CONCLUSIONS. The SNP infusion exerted an important additional stimulus for IL-6 release after relatively mild surgical trauma in both groups. This finding is probably due to the liberation of NO from the SNP molecule and an increase in the intracellular concentration of cGMP. The elevation of the plasma catecholamines immediately after SNP administration should also be taken into account, because an augmentation of the cAMP in various cell types has been proven to result in increased release of IL-6.
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PMID:[Increase in interleukin-6 plasma concentrations following hypotensive anesthesia with sodium nitroprusside]. 761 79

Inflammatory cytokines (interleukin 1 alpha, 1 beta and tumor necrosis factor-alpha) induce the formation of nitrite by C6 astrocytoma cells in a manner that was blocked by inhibitors of NO synthase such as NG-monomethylarginine. They increase the formation of cGMP. This action was potentiated by isobutylmethylxanthine and was inhibited by NG-monomethylarginine. Interleukin-6 and interferon-gamma were inactive. It is concluded that the nitridergic signalling pathway is active in C6 cells and is a major target for inflammatory cytokines.
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PMID:IL1 and TNF alpha induce cGMP formation in C6 astrocytoma cells via the nitridergic pathway. 768 59

Our objective was to investigate the direct effect of interleukin-6 (IL-6) on the vascular smooth muscle contraction. We measured the contraction of endothelium-denuded aortic rings isolated from Sprague-Dawley rats. We also investigated the involvement of vasodilator prostaglandin and guanosine 3',5'-cyclic monophosphate (cGMP) productions in the effect of IL-6 using cultured rat vascular smooth muscle cells (VSMC). Exposing the aortic rings to recombinant murine IL-6 (50 U/ml) for 180 min significantly suppressed the phenylephrine (10(-9)-10(-5) M)-induced contraction. This inhibitory effect of IL-6 on the contraction tended to exhibit a dose-dependent relationship (0.5-50 U/ml). The effect of IL-6 was totally eliminated in the presence of indomethacin (10(-5) M). The release of immunoreactive 6-ketoprostaglandin F1 alpha from cultured rat VSMC was significantly increased by exposure to IL-6. Intracellular cGMP concentration in VSMC was not affected by IL-6. In conclusion, IL-6 is a potent inhibitor of the alpha-adrenergic-stimulated contraction of vascular smooth muscle. Its action is endothelium independent and mediated by the increased synthesis of prostacyclin in VSMC.
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PMID:Inhibitory effect of interleukin-6 on vascular smooth muscle contraction. 816 Aug 37

The effects of a 26 kDa protein isolated from vertebrate retina rod outer segments (ROS) and its reconstituted analog on the phosphodiesterase (PDE) activity and cGMP-dependent conductance have been studied [Nature 313 (1985) 310-313]. Using the patch-clamp technique it was shown that the 26 kDa protein in concentrations up to 1 microM accelerates hydrolysis of cGMP by near-membrane PDE by 1-2 orders of magnitude. This process is suggested to be mediated by some intracellular agent. At the same concentrations the 26 kDa protein was shown to inhibit cGMP-dependent conductance of the photoreceptor membrane. A possible role of these effects in the processes of phototransduction and adaptation is discussed.
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PMID:On the activation of phosphodiesterase by a 26 kDa protein. 838 Jul 75

We examined the effect of interleukin-6 on the levels of cGMP and nitrite in rat hippocampal slices. Interleukin-6 at 400 ng/ml time dependently increased the content of cGMP of slices after incubation for 1, 2, 3, and 4 h, and the effect of interleukin-6 was maximal at 2 h post-incubation. In addition, exposure of slices to interleukin-6 at 80, 400 and 2000 ng/ml or at 16, 80 and 400 ng/ml for 2 h significantly elevated the cGMP level and nitrite level, respectively, in a concentration-dependent manner. Also, 0.1 mM NG-nitro-L-arginine alone showed no effect on either the cGMP level or the nitrite level. However when incubated in conjunction with 400 ng/ml interleukin-6 for 2 h, NG-nitro-L-arginine apparently prevented the increase in cGMP and nitrite induced by 400 ng/ml interleukin-6. The present results show that NO mediates the increase in cGMP induced by interleukin-6 and suggest that interleukin-6 may exert an inducible effect on the NO synthase in hippocampal slices.
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PMID:Interleukin-6 increases the levels of cyclic GMP and nitrite in rat hippocampal slices. 908 46

We studied the effects of C-type natriuretic peptide (CNP) on rat cultured mesangial cell proliferation. (1) Exposure to CNP (10 nM-1 microM for 72 h) inhibited [3H]thymidine incorporation into mesangial cells in a concentration-dependent manner. Atrial natriuretic peptide (1 nM-1 microM), a peptide related to CNP, also decreased [3H]thymidine incorporation into these cells in a concentration-dependent manner. (2) Both CNP (10 nM- microM) and atrial natriuretic peptide (10 nM-1 microM) also decreased mesangial cell number. (3) The cyclic GMP analog, 8-bromo-cyclic GMP (100 microM and 1 microM), mimicked the inhibitory effects of CNP and atrial natriuretic peptide on [3H]thymidine incorporation into mesangial cells, whereas inhibitors of protein kinase C, protein kinase A, and protein kinase G reduced the effect of both natriuretic peptides. Moreover, the phosphatase inhibitor, calyculin A, increased [3H]thymidine incorporation into mesangial cells. (4) CNP and atrial natriuretic peptide decreased interleukin-1-, interleukin-6-, platelet derived growth factor-, angiotensin II-induced [3H]thymidine incorporation into mesangial cells. These results suggest that CNP exerts inhibitory effects on mesangial cell proliferation and that this effects depend on protein phosphorylation pathways.
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PMID:C-type natriuretic peptide inhibits rat mesangial cell proliferation by a phosphorylation-dependent mechanism. 945 75

NCX4016 (2 acetoxy-benzoate 2-(2-nitroxymethyl)-phenyl ester, NicOx S.A., France) is an anti-thrombotic agent, chemically related to acetylsalicylic acid (ASA) and able to release NO. We tested the effects of NCX4016 and ASA on the release of the thromboxane (TX) A(2) metabolite TXB(2), tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), expression and activity of tissue factor (TF) in stimulated, adherent human monocytes. Both ASA and NCX4016 1 - 1000 micromol l(-1) dose-dependently reduced TXB(2) concentration, measured by RIA in the supernatant of 10 microg ml(-1) LPS-stimulated cells. NCX4016 activity was comparable to that of equimolar ASA when incubation lasted 6 h (NCX4016 30 micromol l(-1): -86.0+/-10.1%, NCX4016 300 micromol l(-1): -92.2+/-9.0%, ASA 30 micromol l(-1): -92.3+/-7.5%, ASA 300 micromol l(-1): -97.3+/-1.0%, n=6, M+/-s.d.). Most of the activity of NCX4016 up to 100 micromol l(-1) was prevented by 10 micromol l(-1) ODQ, inhibitor of cyclic GMP. NCX4016 100 - 300 micromol l(-1) reduced TNF-alpha (NCX4016 300 micromol l(-1)=-77.2+/-19.9%, n=6) and IL-6 (NCX4016 300 micromol l(-1): -61.9+/-15.2%, n=6) in LPS stimulated monocytes while ASA had no significant effects. TF activity (NCX4016 300 micromol l(-1): 53.7+/-39.9%, n=4) and immunoreactive TF (NCX4016 300 micromol l(-1): -93.9+/-7.9%, n=7), measured in the supernatant of stimulated cells, were also dose-dependently inhibited by NCX4016 but not by ASA. The present results indicate that NCX4016 inhibits TXA(2) generation as well as cytokine release and TF in human monocytes partly via NO-dependent mechanisms. NCX4016 may have a favourable profile of activities in the clinical setting of athero-thrombosis.
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PMID:NCX4016 (NO-Aspirin) has multiple inhibitory effects in LPS-stimulated human monocytes. 1160 32


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