Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:031927 (cytokine)
 144,509 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the effect of cytokine priming by recombinant human tumour necrosis factor alpha (rhTNF alpha) on the release of vasoactive mediators from human polymorphonuclear leukocytes (PMNs). Supernatants of human PMNs (100 microliters, 5 x 10(7) ml, from 12 donors) relaxed precontracted rabbit aortic rings. The relaxations were preceded by a transient contraction in four experiments. In contrast, supernatants of PMNs incubated with rhTNF alpha (0.3 nM, 30 min, 37 degrees C) elicited variable vascular responses that consisted of either a sustained contraction (n = 4), a transient contraction followed by a sustained relaxation (n = 2), or a sustained relaxation only (n = 6). The vascular tone produced by the rhTNF alpha-treated PMN supernatant was significantly greater over 30 min than that produced by the control supernatant (p < 0.01). Endothelium removal prevented the PMN-induced contractions and significantly decreased the vascular tone produced by all rhTNF alpha-treated PMN supernatants (p < 0.05). The PMN supernatants had no vasoactive effect on aortic rings at resting tension. Molecular size analysis indicated that the PMN-derived contractile mediator is > 30,000 Da. These results suggest that human PMNs, primed by rhTNF alpha, release a stable endothelium-dependent vasoconstrictor that opposes the action of a stable, spontaneously released direct vasodilator.
J Cardiovasc Pharmacol 1992
PMID:Tumour necrosis factor alpha augments the release of an endothelium-dependent vasoconstrictor from human polymorphonuclear leukocytes. 128 Jul 46

The aim of the present experiments was to test the possible involvement of nitric oxide (NO) in cytokine-induced enhancement of tumor cell (TC) adhesion to endothelial cells (ECs). Exposure of EA hyb 926 cells to TNF (500 U/ml) plus IFN (100 U/ml) for 24 h significantly enhanced their adhesivity for the 51Cr-labeled GLC1 (small cell lung carcinoma) TCs. Conversely, exposure of TCs to cytokines did not result in an increased adhesion of these cells to ECs. TC-stimulated adhesion to EA hyb 926 was abrogated by the glucocorticoid dexamethasone (Dex, 10(-7) M), the NO synthase inhibitors N omega-nitro-L-arginine methyl ester (L-NAME, 10(-5) M) and NG-monomethyl-L-arginine (L-NMMA, 10(-5) M) and the protein synthesis inhibitor cycloheximide (Cex, 10(-6) M). Furthermore, GLC1-stimulated adhesion to EA hyb 926 was reversed following removal of L-arginine from the medium or pretreatment with the guanylate cyclase inhibitor methylene blue. TC-stimulated adhesion was also prevented when TCs were pretreated with the monoclonal antibody CD15 directed against the endothelial-leukocyte adhesion molecule (ELAM-1) ligand or following exposure of ECs to anti-ELAM-1 monoclonal antibody. Although suppressing TC-stimulated adhesion, L-NMMA failed to modify significantly cytokine-induced ELAM-1 expression in EA hyb 926. These results (a) provide evidence for the NO-inducible pathway contributing to cytokine-induced enhancement of tumor cell adhesion to the vascular endothelium and (b) demonstrate the involvement of the ELAM-1/CD15 adhesion system in tumor cell-stimulated adhesion to ECs.
J Cardiovasc Pharmacol 1992
PMID:Involvement of nitric oxide in tumor cell adhesion to cytokine-activated endothelial cells. 128 56

Nitric oxide (NO) is synthesized in vascular endothelial cells, and appears to play an important role in the control of blood pressure and platelet aggregation. A detailed understanding of the regulation of NO synthesis by endothelial cells has been hampered by the lack of molecular clones for endothelial NO synthase; we now report the isolation and characterization of such clones. The constitutive NO synthases present in endothelial cells and in brain share common biochemical and pharmacologic features. We purified NO synthase from bovine brain, and determined the amino acid sequence of several tryptic peptides. These sequence data were utilized to design PCR-generated NO synthase cDNA probes, which were used to isolate clones encoding NO synthase from a bovine aortic endothelial cell (BAEC) cDNA library. A full-length NO synthase cDNA clone was isolated, representing a protein of 1,205 amino acids with a molecular mass of 133 kDa. The deduced amino acid sequence of the BAEC NO synthase cDNA differs at numerous residues from the sequence determined for the purified bovine brain protein, and shows 50-60% sequence identity with recently isolated molecular clones for murine macrophage and rat brain NO synthase isoforms. Bovine genomic Southern blots probed with bovine brain and BAEC NO synthase cDNA probes identify distinct bands, indicating that these cDNAs are the products of different genes. Prolonged treatment of BAEC with the cytokine TNF alpha, which results in a marked increase in NO synthase activity, is associated with a decrease in the abundance of the 4.8-kb BAEC NO synthase transcript.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1992
PMID:Molecular cloning of constitutive endothelial nitric oxide synthase: evidence for a family of related genes. 128 83

Analysis of the conditioned medium from cultured human heart valves showed that these tissues secrete a biologically active factor that induces chondrocytes in cultured cartilage to degrade extracellular matrix proteoglycan. This activity was similar to that described for porcine interleukin-1 (catabolin) and a cytokine secreted by cultured porcine heart valves (cardiac catabolic factor). The biological activity of the material in human valve conditioned medium was unaffected by the presence of low doses of cortisol, but its production by cultured valves was impaired by this steroid or benoxaprofen and abolished by cycloheximide. Addition of the conditioned medium to fibroblast monolayers stimulated the secretion of prostaglandin E and the tissue inhibitor of metalloproteinases (TIMP) but not collagenase. Preincubation of the conditioned medium with antiserum raised to the acidic form of porcine interleukin-1 neutralised the proteoglycan degrading stimulus. The material is biologically similar to other cytokines and antigenically related to porcine interleukin-1.
Cardiovasc Res 1987 Jan
PMID:Production of a factor by cultured human heart valves that is immunologically related to interleukin 1. 349 25

We wished to test the hypothesis of a connection existing between inducible nitric oxide (NO) synthesis and production of extracellular matrix proteins in endothelial cells (EC). We recently reported that the inducible-NO pathway contributes to cytokine-induced enhancement of tumor cell (TC) adhesion to cultured vascular endothelium, independent of changes in E-selectin expression on endothelial cells (EC). We now show that inducible NO-synthase is involved in enhancing fibronectin production by EC. Indeed, fibronectin synthesis and secretion increased both in the EA.hy926 EC line and in human umbilical vein EC (HUVEC) after prolonged exposure to tumor necrosis factor-alpha (TNF-alpha) or interferon-gamma (IFN-gamma). This effect was reversed by the reported inhibitor of NO synthase N omega-nitro-L-arginine methyl ester (L-NAME 10(-5) M). The two cytokines exerted no additive effect, suggesting that they trigger a common metabolic pathway. NO production by cytokine-stimulated EC was dependent on the inducible NO-pathway, as demonstrated by studies of EC-dependent inhibition of platelet aggregation. This inhibition was also evident in calcium-free medium and was reversed by L-NAME and by two inhibitors of protein synthesis that are reported to block the inducible-NO synthase, such as dexamethasone (Dex 10(-7) M) and cycloheximide (Chx 10(-6) M). We conclude that modulation of the inducible NO-synthase may regulate matrix protein production by vascular endothelium during inflammation.
J Cardiovasc Pharmacol 1994 Dec
PMID:Inducible nitric oxide synthase modulates fibronectin production in the EA.hy926 cell line and cultured human umbilical vein endothelial cells. 753 52

So that changes in production and binding of tumor necrosis factor-alpha during postpneumonectomy lung growth could be determined, rats underwent left lung resection and were killed 3, 7, or 14 days later, 1 hour after the injection of 3H-thymidine. Serum was collected, and the lungs were lavaged and perfused in vitro. Lung volumes were measured. Lungs were homogenized, and changes in lung weight, protein content, deoxyribonucleic acid content, deoxyribonucleic acid synthesis, and tyrosine kinase activity of different lobes were recorded. Tumor necrosis factor-alpha content of serum, lavage fluid, and perfusate was measured by an enzyme-linked immunoassay. The binding of tumor necrosis factor-alpha to membrane extracts of lung homogenates was measured by immunoblots. Whereas the cardiac lobe of the remaining right lung demonstrated larger increases in size than other lobes after pneumonectomy, there was no difference in any growth parameter between it and the other lung lobes. Serum tumor necrosis factor-alpha was detectable in sham-operated animals and increased significantly after pneumonectomy. However, by day 14, it was not different from the level in sham-operated animals. In contrast, tumor necrosis factor-alpha in lavage fluid remained significantly elevated, and its binding increased gradually throughout the study period. Tumor necrosis factor-alpha in perfusate did not demonstrate any rise. We conclude that lung growth after pneumonectomy is uniform among various lobes, which suggests that it is regulated by humoral factors. Because tumor necrosis factor-alpha, a cytokine known to stimulate cellular proliferation and matrix synthesis, is produced and bound to the lung during this process, it may be one of the humoral factors implicated in postpneumonectomy lung growth.
J Thorac Cardiovasc Surg 1995 Aug
PMID:Changes in tumor necrosis factor in postpneumonectomy lung growth. 763 58

The proinflammatory cytokines have been implicated in mediating myocardial dysfunction associated with myocardial infarction, severe congestive heart failure, and sepsis. We tested the hypothesis that cytokine levels are elevated after uncomplicated coronary artery bypass grafting and associated with episodes of postoperative myocardial ischemia and dysfunction. Coronary artery bypass grafting was performed under general anesthesia with moderate systemic hypothermia and cold-blood potassium cardioplegic solution. Tumor necrosis factor-alpha and interleukin-6 levels were determined by bioassays, and interleukin-8 levels were measured by a sandwich enzyme-linked immunosorbent assay. Myocardial function and ischemic episodes were assessed by intraoperative transesophageal echocardiography and perioperative 12-channel Holter monitoring. A total of 22 patients were studied, with no deaths or complications. Arterial tumor necrosis factor-alpha rose in a bimodal distribution, peaking at 2 and 18 to 24 hours after the operation (at 20.2 +/- 6.4 pg/ml, [mean +/- standard error of the mean]) and 5.8 +/- 1.6 pg/ml, respectively; before cardiopulmonary bypass: 0.90 +/- 0.20 pg/ml, p < 0.001 for both peaks) then progressively declined to levels before bypass. Arterial interleukin-6 was maximally elevated immediately on termination of cardiopulmonary bypass and peaked again 12 to 18 hours after cardiopulmonary bypass (at 7520 +/- 2439 pg/ml and 6216 +/- 1928 pg/ml, respectively; before bypass: 746 +/- 187 pg/ml, p < 0.0001 for both peaks). Arterial interleukin-8 levels were more variable but followed a similar pattern, peaking in the early period after cardiopulmonary bypass and again at 16 to 18 hours after the operation (at 4110 +/- 1403 pg/ml and 1760 +/- 1145 pg/ml, respectively; before bypass: 461 +/- 158, p < 0.05 for both peaks). By multivariate analysis, the aortic crossclamp time was independently predictive of postoperative cytokine levels. Left ventricular wall motion abnormalities were associated with both interleukin-6 and interleukin-8 levels, worsening scores being associated with increasing levels (for interleukin-6, p = 0.003; for interleukin-8, p = 0.05). Postoperative myocardial ischemic episodes were associated with interleukin-6 levels, six of seven (85%) patients with episodes of myocardial ischemia after a peak in interleukin-6 concentrations (p < 0.01). We conclude that proinflammatory cytokines are elevated after uncomplicated coronary revascularization and may contribute to postoperative myocardial ischemia and segmental wall motion abnormalities.
J Thorac Cardiovasc Surg 1994 Oct
PMID:Relationship of the proinflammatory cytokines to myocardial ischemia and dysfunction after uncomplicated coronary revascularization. 793 95

To determine the cytokine release during normothermic cardiopulmonary bypass, we have measured plasmatic levels of tumor necrosis factor-alpha and interleukins-1 beta, 6, and 8 in 10 patients during the first 24 hours after the start of bypass. Arterial blood samples were collected at intervals before, during, and after bypass. Interleukin-1 beta was not detectable in the plasma, and traces of tumor necrosis factor-alpha were detected in only three patients at times independent of the cardiopulmonary bypass procedure. Circulating endotoxin remained undetectable. Plasma interleukin-6 and interleukin-8 rose significantly from 2 until 24 hours after the start of bypass (p < 0.05) and peaked respectively at 4 and 2 hours after the beginning of bypass (interleukin-6, 268.1 +/- 131.43 pg/ml; interleukin-8, 370 +/- 420 pg/ml; mean peak +/- standard deviation). Peak values of interleukin-6 and interleukin-8 were correlated neither with the duration of aortic crossclamping or the bypass procedure nor with the hemodynamic parameters recorded at the same times. This study shows that normothermic cardiopulmonary bypass does not induce systemic release of tumor necrosis factor-alpha and interleukin-1 beta. A local production of these cytokines cannot be excluded, because interleukin-6 and interleukin-8 are produced by stimulated macrophages and monocytes in response to tumor necrosis factor-alpha and interleukin-1 beta. Our results, at normothermia, show a similar pattern of interleukin-6 and interleukin-8 release when compared with release during hypothermic cardiopulmonary bypass. Interleukin-8, an important chemotactic neutrophil factor, might play a role in reperfusion injuries observed in lungs and heart after cardiopulmonary bypass.
J Thorac Cardiovasc Surg 1994 Oct
PMID:Circulating cytokines in patients undergoing normothermic cardiopulmonary bypass. 793 96

Patients undergoing cardiopulmonary bypass are known to develop whole body inflammation that often results in a characteristic syndrome early postoperatively. This phenomenon has been attributed to complement activation caused by exposure of blood to the foreign surfaces of the cardiopulmonary bypass circuit. It has been unknown if cytokines are involved. Plasma levels of complement activation products (C3a, C4a, C5a, and C5b-9), interleukins (IL-1 beta, IL-2, IL-4, and IL-6), and tumor necrosis factor-alpha were measured at multiple time points before, during, and after cardiopulmonary bypass in 29 patients. No significant increase over preinduction levels was seen in the cytokines except for IL-6, which was significantly increased during cardiopulmonary bypass (p < 0.001), reaching a maximum 3 hours after cardiopulmonary bypass. C3a, C4a, and C5b-9 levels were significantly elevated during cardiopulmonary bypass (p < 0.001), with maximum C5b-9 levels preceding the IL-6 elevation. Heparin coating of the cardiopulmonary bypass circuit was not demonstrated to have an effect on activation of complement or cytokine production. There was no statistically significant correlation among hemodynamic variables or pulmonary function and complement, interleukin, or tumor necrosis factor-alpha levels. These results confirm the presence of complement activation and demonstrate the production of IL-6 after the generation of C5b-9 in patients undergoing cardiopulmonary bypass. IL-6 may contribute to adverse systemic reactions associated with cardiopulmonary bypass.
J Thorac Cardiovasc Surg 1993 Dec
PMID:Cytokine and complement levels in patients undergoing cardiopulmonary bypass. 824 32

Peripheral vasodilation is a common feature of warm heart surgery and creates clinical concerns when pressor agents become necessary because of the potential for some of these drugs to adversely affect flow through newly engrafted arterial and venous bypass conduits. The possible role of a temperature-dependent production of cytokines in the pathogenesis of this vasodilation was investigated in a two-part study. In part I, lipopolysaccharide-activated peritoneal rabbit macrophages (5 x 10(6)/ml) were incubated at 30 degrees or 37 degrees C up to 9 hours and the concentration of tumor necrosis factor released in the supernatant was serially measured by a bioassay. Tumor necrosis factor production was found to increase over time for each of the two temperatures of incubation but was significantly higher throughout the observation period in normothermic experiments than in those done at 30 degrees C. Part II was a prospective clinical study involving 30 patients who underwent either cold (core temperature 28 degrees to 30 degrees C, n = 15) or warm (37 degrees C, n = 15) cardiopulmonary bypass and in whom serum levels of tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 were measured by enzyme-linked immunosorbent assays at 2, 4, 10, and 24 hours after bypass. Cytokine levels were found to be consistently higher in patients having normothermic bypass. Differences between the two groups were significant 2 hours after bypass for tumor necrosis factor alpha and interleukin-6 (p < 0.02 and p = 0.0001, respectively) and 4 and 10 hours after bypass for interleukin-1 beta (p < 0.01 and p < 0.04, respectively). The incidence of vasodilation necessitating vasopressor support was twofold higher in the normothermic group (six patients versus three in the hypothermic group). Taken as a whole, patients supported by pressor agents had significantly higher cytokine levels after bypass than those who did not require pressor therapy. Our results suggest that vasodilation occurring with warm heart operation is, at least partly, mediated by a temperature-dependent release of cytokines. Vasodilation might therefore be mitigated by simply allowing the core temperature to drift during bypass. Our recent clinical experience suggests that this "tepid" heart surgery (32 degrees to 34 degrees C) effectively blunts most of the vasodilatory response to strictly normothermic bypass without compromising maintenance of myocardial aerobiosis during arrest.
J Thorac Cardiovasc Surg 1994 Jan
PMID:A potential mechanism of vasodilation after warm heart surgery. The temperature-dependent release of cytokines. 828


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