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

Lipoprotein (a) (Lp(a)) is a low density lipoprotein-like particle which contains the plasminogen-like apolipoprotein a. Lp(a) levels are elevated in patients with atherosclerotic coronary artery disease. Recent studies suggest that Lp(a) competitively inhibits plasminogen binding to the endothelial cell and interferes with surface-associated plasmin generation. In this study, we present evidence for the presence of Lp(a) in the microvasculature of inflamed tissue. In addition, we demonstrate that Lp(a) regulates endothelial cell synthesis of a major fibrinolytic protein, plasminogen activator inhibitor-1 (PAI-1). In cultured human endothelial cells, Lp(a) enhanced PAI-1 antigen, activity, and steady-state mRNA levels without altering tissue plasminogen activator activity or mRNA transcript levels. This effect was cell-specific. Although other lipoproteins did not coordinately raise PAI-1 mRNA levels in endothelial cells, low density lipoprotein treatment selectively raised the level of the 3.4-kilobase mRNA species of PAI-1 without a concomitant increase in PAI-1 activity or antigen. Endothelial cell exposure to Lp(a) did not cause generalized endothelial cell activation since the functional activity and mRNA levels for tissue factor, platelet-derived growth factor and interleukin-6 were not elevated following Lp(a) exposure. These data suggest a molecular mechanism whereby Lp(a) may support a specific prothrombotic endothelial cell phenotype, namely by increasing PAI-1 expression.
 ...
PMID:Lipoprotein (a) regulates plasminogen activator inhibitor-1 expression in endothelial cells. A potential mechanism in thrombogenesis. 182 42

A glycoprotein (Mr = 43,000) from horseshoe crab hemocytes with antimicrobial activity against Gram-negative bacteria was purified. The internal peptide sequences coincided exactly with the deduced amino acid sequence of a cDNA clone, designated limulus factor D, which was isolated by screening a hemocyte cDNA library with an anti-human plasminogen antibody. The open reading frame codes for a precursor of factor D of 394 amino acid residues, including an NH2-terminal signal sequence. The COOH-terminal domain of factor D has significant sequence homology with the catalytic domain of mammalian serine proteases, in particular with human tissue plasminogen activator (32% identity), except for the substitution of Ser of the active site triad to Gly. Factor D has a unique NH2-terminal domain with weak sequence homology with part of the mammalian interleukin-6 receptor alpha-chain. Factor D is likely to have an important role in host defense mechanisms.
 ...
PMID:Limulus factor D, a 43-kDa protein isolated from horseshoe crab hemocytes, is a serine protease homologue with antimicrobial activity. 897 95

All previous in vitro biocompatibility tests of peritoneal dialysis fluids have shown that these have inhibitory effects on the function of peritoneal mesothelium. This report presents results from in vitro experiments performed to study the effect of dialysis fluids (Dianeal 1.36 and Dianeal 3.86; Baxter, Round Lake, IL) on the function of mesothelial cells under conditions that simulate the in vivo state of these solutions in the peritoneal cavity. Thus, cells were initially exposed only to the unused fluids that were thereafter gradually diluted (over 4 hours) with pooled effluent dialysate from continuous ambulatory peritoneal dialysis patients. During the following 20 hours, cells were incubated in a mixture of unused fluid (10% vol/vol) and dialysate effluent (90% vol/vol). The mesothelial cells exposed to dialysis fluids under such conditions became activated cells compared with exposed to dialysate effluent (control) alone. Thus, synthesis by mesothelial cells of all tested substances was enhanced during exposure of the mesothelium to the dialysis fluids: interleukin-6: Dianeal 1.36, +257%; Dianeal 3.86, +181% (both P < 0.05); hyaluronic acid: Dianeal 1.36, +72%; Dianeal 3.86, +63% (both P < 0.05); tissue plasminogen activator: Dianeal 3.86, +33% (P < 0.05); and plasminogen activator/inhibitor-1: Dianeal 1.36, +28%; Dianeal 3.86, +38% (both P < 0.05). Our results show that the peritoneal mesothelium becomes activated when it is exposed to acidic, hyperosmotic dialysis fluids diluted with the dialysate effluent, in a manner that imitates the in vivo changes in these solutions during their intraperitoneal dwell.
 ...
PMID:In vitro simulation of the effect of peritoneal dialysis solution on mesothelial cells. 904 Dec 17

High plasma fibrinogen appears to be an important risk factor for the development of atherosclerosis. The aim of our study was to measure fibrinogen and fibrin degradation products (D-dimer), interleukin-6 tissue plasminogen activator, plasminogen activator inhibitor-1 and urokinase-type plasminogen activator in the plasma and arterial walls of 45 patients who had arterial surgery between April 1993 and November 1995. The arterial specimens were also examined by immunohistochemists for these same factors. The serum fibrinogen and fibrin degradation products were high in all patients, and fibrinolysis was depressed. Few leukocytes were seen in the arterial walls, which had poor fibrinolytic activity. Plasminogen-activator inhibitor activity in the wall was also reduced in the affected arterial walls. The abdominal aorta appeared to have the highest levels of fibrinogen and this may be related to its ability to form aneurysms. Fibrinogen may play an important role in the progression of atherosclerotic disease.
 ...
PMID:Fibrinogen and fibrinolysis in blood and in the arterial wall: its role in advanced atherosclerotic disease. 979 64

Disruption of atherosclerotic plaques with associated thrombus is responsible for the majority of the acute coronary syndromes. Plaque instability is related closely to the degree of inflammation. Inflammatory cells within the plaque produce cytokines that inhibit collagen production by vascular smooth muscle cells and increase the production of metalloproteinases, which degrade the extracellular matrix in the fibrous cap. The recruitment of inflammatory cells into the vessel wall occurs in a coordinated sequence of events involving the expression of cellular adhesion molecules on the surface of activated endothelial cells and the production of chemoattractants, and occurs in part in response to oxidation of low-density lipoprotein within the vessel wall. The cellular adhesion molecules are shed into the circulating blood in several disease states, including clinically evident atherosclerosis. The acute-phase reactants C-reactive protein and interleukin-6, and markers of the fibrinolytic state (plasminogen activator inhibitor-1 and tissue plasminogen activator), are also elevated in the acute coronary syndromes and in healthy individuals at increased risk for developing coronary artery disease. These markers may reflect vascular inflammation and thereby the stability of atherosclerotic plaques. Their measurement may pinpoint the mechanisms of benefit of cholesterol-lowering therapy and other interventions designed to reduce coronary risk, and potentially could offer a new method for monitoring coronary risk factor reduction in patients.
 ...
PMID:Inflammation, the endothelium, and the acute coronary syndromes. 988 50

C-reactive protein, a hepatic acute phase protein largely regulated by circulating levels of interleukin-6, predicts coronary heart disease incidence in healthy subjects. We have shown that subcutaneous adipose tissue secretes interleukin-6 in vivo. In this study we have sought associations of levels of C-reactive protein and interleukin-6 with measures of obesity and of chronic infection as their putative determinants. We have also related levels of C-reactive protein and interleukin-6 to markers of the insulin resistance syndrome and of endothelial dysfunction. We performed a cross-sectional study in 107 nondiabetic subjects: (1) Levels of C-reactive protein, and concentrations of the proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, were related to all measures of obesity, but titers of antibodies to Helicobacter pylori were only weakly and those of Chlamydia pneumoniae and cytomegalovirus were not significantly correlated with levels of these molecules. Levels of C-reactive protein were significantly related to those of interleukin-6 (r=0.37, P<0.0005) and tumor necrosis factor-alpha (r=0.46, P<0.0001). (2) Concentrations of C-reactive protein were related to insulin resistance as calculated from the homoeostasis model assessment model, blood pressure, HDL, and triglyceride, and to markers of endothelial dysfunction (plasma levels of von Willebrand factor, tissue plasminogen activator, and cellular fibronectin). A mean standard deviation score of levels of acute phase markers correlated closely with a similar score of insulin resistance syndrome variables (r=0.59, P<0.00005), this relationship being weakened only marginally by removing measures of obesity from the insulin resistance score (r=0.53, P<0.00005). These data suggest that adipose tissue is an important determinant of a low level, chronic inflammatory state as reflected by levels of interleukin-6, tumor necrosis factor-alpha, and C-reactive protein, and that infection with H pylori, C pneumoniae, and cytomegalovirus is not. Moreover, our data support the concept that such a low-level, chronic inflammatory state may induce insulin resistance and endothelial dysfunction and thus link the latter phenomena with obesity and cardiovascular disease.
 ...
PMID:C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? 1019 25

The aim of this study was to see if a short-term period of exposure to cold in young healthy subjects causes changes in hematological factors known to be associated with the promotion of thrombogenesis. Over a period of 48 hours, changes in the distribution of erythrocytes, granulocytes, and blood platelets, as well as several coagulation, inflammatory, and fibrinolytic parameters, were monitored in 11 young healthy male subjects following a short period (1 hour) of cold exposure (CE) (ambient temperature, 11 degrees C) or exposure to thermoneutral conditions (ambient temperature, 26 degrees C) in winter (November). The major findings were: (1) a CE-induced hemoconcentration as indicated by an increase in erythrocyte count (3.2% increase); (2) after appropriate adjustments for changes in hemoconcentration, a cold-induced mobilization of granulocytes (14.5% increase) and a cold-induced decrease in lymphocytes (7% decrease); (3) thromboxane B2 release following endotoxin stimulation of whole blood was increased by 27.4% in the CE experiments; (4) diurnal rhythms were observed in granulocytes, blood platelets, middle plate volume, tissue plasminogen activator, and plasma activator inhibitor; and (5) CE caused no significant changes in lipopolysaccharide-induced tissue factor, nor in the blood coagulation factor VII or cytokines, interleukin-6, and tumor necrosis factor. It is concluded that short-term cold exposure in young healthy subjects initiates a mild inflammatory reaction and a tendency for an increased state of hypercoagulability.
 ...
PMID:The effect of short-term cold exposure on risk factors for cardiovascular disease. 1041 98

Intra-arterial desmopressin caused dose and time dependent increases (p <0.001 for all) in forearm blood flow (all doses) and plasma tissue plasminogen activator (t-PA) concentrations (desmopressin > or = 70 ng/min). Although plasma t-PA concentrations rose in both forearms, there was a modest local release of t-PA in the infused forearm (14 ng/100 mL of tissue/min, p <0.05). At desmopressin doses > or = 300 ng/min, plasma von Willebrand factor (vWf) and Factor VIII:C concentrations rose in both forearms (p <0.001) and correlated with the rise in interleukin-6 concentrations (r = 0.92, p <0.001: r = 0.85, p = 0.002 respectively). Neither desmopressin nor substance P caused t-PA, vWf or Factor VIII:C release in the patients, although desmopressin increased plasma interleukin-6 concentrations as in healthy volunteers. We conclude that desmopressin releases t-PA, vWf and Factor VIII:C predominantly via systemic mechanisms, possibly mediated by cytokine release. Patients with type 3 vWD appear to have a generalised failure to release t-PA acutely despite a normal interleukin-6 response to desmopressin infusion.
 ...
PMID:Local and systemic effects of intra-arterial desmopressin in healthy volunteers and patients with type 3 von Willebrand disease. Role of interleukin-6. 1095 89

This study investigated the contribution of endogenous suppression of fibrinolysis and increased fibrin deposition to intestinal dysfunction and injury in a rat model of intestinal ischemia/reperfusion (I/R), as fibrinolytic inhibition may lead to thrombotic obstructions that compromise microcirculation and promote intestinal injury. Circulatory fibrinolysis was enhanced by intravenous administration of recombinant tissue plasminogen activator (rt-PA) or by inhibition of PAI-I by administration of MA-33H1F7. Coagulation and fibrinolysis parameters obtained from portal blood were correlated to fibrin deposition (determined by anti-rat fibrin antibody staining), intestinal function (glucose/water clearance) and intestinal injury (histological evaluation by Park/Chiu score). Enhanced circulatory fibrinolytic activity, as evidenced by increased portal plasma plasminogen activator activity, elevated fibrin degradation products and decreased levels of PAI-I, did not reduce mucosal fibrin deposition and microthrombosis in postischemic intestinal tissue. Furthermore, rt-PA or anti-PAI-I antibody administration did not attenuate I/R-induced intestinal injury or dysfunction, as demonstrated by intestinal histopathology scores of 4.8+/-0.2 and 4.7+/-0.3 (control I/R group 4.7+/-0.2) and glucose clearances of 47+/-6 and 46+/-9 micro L/min g (control I/R group 30+/-8 micro L/min. g) after 40 minutes of intestinal ischemia and 3 hours of reperfusion, respectively. However, both interventions resulted in decreased levels of interleukin-6, which may indicate fibrin-induced modulation of inflammation. Attempts to enhance the fibrinolytic activity (either by rt-PA or by anti-PAI-I administration), indicated by increased portal plasma levels of released FDP, failed to decrease mucosal fibrin deposition and to attenuate intestinal I/R injury. Based on our observations and previous reports, the contribution of suppressed endogenous fibrinolysis to microcirculatory fibrin deposition and I/R-injury may be of limited importance.
 ...
PMID:Enhancement of endogenous fibrinolysis does not reduce local fibrin deposition, but modulates inflammation upon intestinal ischemia and reperfusion. 1498 25

The effects of cerivastatin and fenofibrate on proteins involved in haemostasis and on markers of inflammation were investigated in otherwise healthy middle-aged males with combined hyperlipidemia. Besides classical risk factors, other so-called novel risk factors for coronary artery disease are seen to be playing an increasingly important role in the development and progression of atherosclerosis. Thirty-eight males, aged 49 +/-5 years were randomised to 12 weeks treatment either with cerivastatin at a daily dose of 0.2 mg to 0.4 mg to achieve the LDL cholesterol goal of <3.0 mM, or with fenofibrate 250 mg daily. Fasting serum lipids, homocysteine, total and free tissue factor pathway inhibitor (TFPI), plasminogen activator inhibitor (PAI-1) and tissue plasminogen activator (t-PA) antigen and activity, C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were measured. No change in homocysteine level was observed in the cerivastatin group, while after fenofibrate administration it increased (p <0.0001). Total TFPI decreased significantly after cerivastatin (p = 0.002), but not after fenofibrate. Free TFPI did not decrease after either drug. Neither drug affected (t-PA) antigen and activity, while fenofibrate increased PAI-1 antigen (p <0.05) and activity (p <0.05). Cerivastatin decreased serum CRP values by 49.5% (p = 0.001), and fenofibrate by 29.8% (p = 0.03). The decreases of CRP in the two groups differed significantly (p = 0.04). IL-6 levels decreased significantly in the fenofibrate group (39%; p <0.0001), but not in the cerivastatin group (15%; p = 0.24) No significant decreases were observed for TNF-alpha. Cerivastatin had neutral effects on fibrinolysis, homocysteine or coagulation. On the other hand, fenofibrate increased PAI-1 antigen and activity and homocysteine, and did not affect coagulation. Both cerivastatin and fenofibrate reduced CRP levels, the decrease being significantly greater after cerivastatin. Fenofibrate also significantly decreased IL-6.
 ...
PMID:Statin and fibrate treatment of combined hyperlipidemia: the effects on some novel risk factors. 1554 43


1 2 3 Next >>