Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To understand the pathogenesis of vasculitides, we analyzed how cytokine stimulation of HUVEC in vitro activates the cytotoxic capacity of polymorphonuclear (PMN) granulocytes. IL-1beta, IFN-gamma, or TNF-alpha caused highly significant dose and time-dependent HUVEC injury. TNF-alpha-treated HUVEC activated the PMN by means of phospholipase C-related event, since coincubations conferred PMN to react with a rise of cytosolic calcium concentrations, [Ca2+]i. Ab blockade of ICAM-1 on HUVEC inhibited 50 to 70% of the injury induced by these cytokines, whereas a mAb to E-selectin reduced 45 to 65% of IL-1beta- and TNF-alpha-, but not IFN-gamma-induced cytotoxicity. The role of nitric oxide (NO) was of significance since injury induced by each cytokine was reduced by 60 to 87% by specific NO-synthase inhibitors, as well as by scavenging extracellular NO by oxyhemoglobin. In contrast, injury induced by TNF-alpha was inhibited by neither superoxide dismutase or catalase, alpha1-antitrypsin, alpha2-macroglobulin, nor the platelet-activating factor receptor antagonist WEB-2086. Moreover, PMN from a patient with chronic granulomatous disease were fully capable of mediating cytotoxicity. The possibility that IL-8, produced by HUVEC in response to TNF-alpha, mediated activation of PMN was not corroborated since addition of an IL-8-blocking mAb did not modify HUVEC injury. Nonetheless, the IL-8 mAb (but not WEB-2086) blocked the rise of [Ca2+]i. Thus, in this in vitro model of vasculitis, the effect of IL-1beta, IFN-gamma, and TNF-alpha as promotors of cytokine-mediated neutrophil-dependent injury to HUVEC is a process dependent on expression of adhesion molecules and probably associated with NO produced in the system.
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PMID:Cytokine-induced neutrophil-mediated injury of human endothelial cells. 921 11

Isocyanates may be involved in the development of chronic obstructive airway disease among exposed workers. A short-term exposure to toluene diisocyanate (TDI) at concentrations near the permissible levels was investigated to examine whether there was an association with changes in pulmonary function tests and in potential markers of airway injury and inflammation in bronchial lavage (BL) and bronchoalveolar lavage (BAL). Seventeen subjects without respiratory symptoms (eight smokers and nine nonsmokers) were exposed once to ambient air and once to TDI (5 parts per billion (ppb) for 6 h followed by 20 ppb for 20 min) in a randomized, single-blind sequence. Pulmonary function tests were repeatedly assessed during exposure and BAL was performed 1 h after each exposure. Biochemical studies on lavage fluids included albumin, immunoglobulins, antiproteases (alpha2-macroglobulin and alpha1-proteinase inhibitor), potential indicators of epithelial cell function (secretory component and Clara cell protein), and cytokines (tumour necrosis factor-alpha, interleukin (IL)-4, IL-5, IL-6, and IL-8). Exposure to TDI caused a modest decrease in specific airway conductance (sGaw) (p=0.053) and in maximal expiratory flow at 25% of forced vital capacity (MEF25%) (p=0.015) when compared with ambient air. Exposure to TDI resulted in a slight increase in BAL albumin level (TDI: 26.4+/-12.5 versus air: 21.8+/-8.6 microg x mL(-1), p=0.044) and in BL alpha2-macroglobulin concentration (TDI: 0.07+/-0.061 versus air: 0.05+/-0.04 microg x mL(-1), p=0.021). This study suggests that exposure to low toluene disocyanate concentrations is associated with minimal but detectable changes in airway calibre and in epithelial barrier permeability. The pulmonary effects of long-term exposure to low levels of isocyanates require further investigation.
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PMID:Pulmonary effects of short-term exposure to low levels of toluene diisocyanate in asymptomatic subjects. 1041 18

Our objectives were to study the value of different proteins in the serum and ascitic fluid and assess their potential in discriminating between malignant and nonmalignant ascites in a model that could be developed to aid clinical diagnosis. In all, 57 different measurements (30 in serum and 27 in ascitic fluid) including erythrocyte sedimentation rate, number of white blood cells, cytokines, interleukin-1a (IL-1a), IL-1b, IL-2, IL-6, IL-8, tumor necrosis factor-alpha, immunoglobulins (IgG, IgA, IgM), complement factors C3 and C4, acute-phase proteins such as alpha1-acid glycoprotein, alpha2-macroglobulin, alpha1-antitrypsin, haptoglobin, C-reactive protein, ferritin, ceruloplasmin and transferin, were performed in 61 patients with ascites (25 with malignant exudates, 13 with nonmalignant exudates, and 23 with transudates). Patients with sepsis were excluded. Correlation tests and one-way ANOVAs were used for comparisons between different groups. Discriminant analyses were used to assess the significance of each parameter in the differentiation process. Correct classification of 100% of cases required the use of all 57 ascitic fluid measurements in the model, which was not considered practical in clinical diagnosis. Discriminant analysis showed that five ascitic fluid measurements-total protein, LDH, TNF-alpha, C4, and haptoglobin-were sufficient for a model to correctly classify 89% of cases. Cross-validation showed that 70% of unknown cases were correctly classified using this model. In conclusion, we have shown that five easily taken protein measurements in the ascitic fluid can differentiate to a large extent between cases with ascites and have proposed a relatively simple statistical model with these parameters that could be developed to be extremely useful in the clinical setting.
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PMID:Discrimination between malignant and nonmalignant ascites using serum and ascitic fluid proteins in a multivariate analysis model. 1074 24

The purpose of this study was to determine if interleukin 8 (IL-8) in complex with alpha2-macroglobulin (alpha-2-M) can be taken up by human alveolar macrophages. First, we demonstrated that human alveolar macrophages have receptors for alpha-2-M but not IL-8. The binding of(125)I-labeled alpha-2-M to the cells was specific and saturable, whereas(125)I-labeled recombinant human IL-8 (rhIL-8) did not bind to macrophages. However,(125)I-rhIL-8-alpha-2-M complexes bound to macrophages, and unlabeled alpha-2-M competed for the binding. We then cultured the cells in the presence of(125)I-rhIL-8-alpha-2-M complexes,(125)I-rhIL-8 alone or buffer for 24 h. Macrophages were lysed, and the released radioactivity measured. IL-8 concentrations in supernatants and cells were also measured using an IL-8 ELISA. When the macrophages were incubated with(125)I-rhIL-8-alpha-2-M complexes there was a significant amount of IL-8 associated with the cells. However, this was not the case when the cells were incubated with(125)I- rhIL-8 alone suggesting that only these complexes were taken-up by human alveolar macrophages. Furthermore, the clearance of complexes was specifically inhibited by a monoclonal antibody against the 515-kDa subunit of the alpha-2-M receptor (alpha-2-MR) but not by an isotopic mouse IgG1. The study shows an important clearance mechanism for IL-8 in the lung.
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PMID:Involvement of alpha-2-macroglobulin receptor in clearance of interleukin 8-alpha-2-macroglobulin complexes by human alveolar macrophages. 1088 Feb 51

Matrix metalloproteinases (MMPs) form a family of enzymes with major actions in the remodeling of extracellular matrix (ECM) components. Gelatinase B (MMP-9) is the most complex family member in terms of domain structure and regulation of its activity. Gelatinase B activity is under strict control at various levels: transcription of the gene by cytokines and cellular interactions; activation of the pro-enzyme by a cascade of enzymes comprising serine proteases and other MMPs; and regulation by specific tissue inhibitors of MMPs (TIMPs) or by unspecific inhibitors, such as alpha2-macroglobulin. Thus, remodeling ECM is the result of the local protease load, i.e., the net balance between enzymes and inhibitors. Glycosylation has a limited effect on the net activity of gelatinase B, and in contrast to the all-or-none effect of enzyme activation or inhibition, it results in a higher-level, fine-tuning effect on the ECM catalysis by proteases in mammalian species. Fast degranulation of considerable amounts of intracellularly stored gelatinase B from neutrophils, induced by various types of chemotactic factors, is another level of control of activity. Neutrophils are first-line defense leukocytes and do not produce gelatinase A or TIMP. Thus, neutrophils contrast sharply with mononuclear leukocytes, which produce gelatinase A constitutively, synthesize gelatinase B de novo after adequate triggering, and overproduce TIMP-1. Gelatinase B is also endowed with functions other than cleaving the ECM. It has been shown to generate autoimmune neo-epitopes and to activate pro-IL-1beta into active IL-1beta. Gelatinase B ablation in the mouse leads to altered bone remodeling and subfertility, results in resistance to several induced inflammatory or autoimmune pathologies, and indicates that the enzyme plays a crucial role in development and angiogenesis. The major human neutrophil chemoattractant, IL-8, stimulates fast degranulation of gelatinase B from neutrophils. Gelatinase B is also found to function as a regulator of neutrophil biology and to truncate IL-8 at the amino terminus into a tenfold more potent chemokine, resulting in an important positive feedback loop for neutrophil activation and chemotaxis. The CXC chemokines GRO-alpha, CTAP-III, and PF-4 are degraded by gelatinase B, whereas the CC chemokines MCP-2 and RANTES are not cleaved.
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PMID:Gelatinase B functions as regulator and effector in leukocyte biology. 1140 67

An enzyme-linked immunosorbent assay (ELISA) for rat alpha2-macroglobulin (alpha2M) using a monoclonal antibody was developed, and used to measure alpha2M in sera from rats injected intramuscularly with turpentine oil as an inflammatory agent. The mean concentration of alpha2M gradually increased and peaked 2 days after the turpentine oil injection. The peak alpha2M concentration ranged from 2362-8472 microg/ml (mean 4531 microg/ml), which was 50-290 times higher than the pre-dosing levels of 23-61 microg/ml. In addition, interleukins (IL)-1, IL-2, IL-4, IL-6, IL-8, IL-10, and interferon (IFN)-gamma were measured using commercial ELISA reagent kits. IL-6 and IL-8 increased and peaked 12 h after turpentine oil injection, the levels being 5-51 times and 2-38 times the pre-dosing ones, respectively. The concentrations of IL-1, IL-2, IL-4, IL-10 and IFN-gamma in rats injected with turpentine oil did not change.
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PMID:Serum alpha2-macroglobulin and cytokine measurements in an acute inflammation model in rats. 1194 79

Previous evidence has shown that coronary angioplasty leads to the release of inflammatory mediators. In this study, we sought to characterize the systemic inflammatory response after coronary stent implantation in patients with unstable angina by measuring different protein markers. Peripheral blood samples were taken before and 24 h, 48 h, and 7 days after successful coronary stenting in 58 patients. Several markers of acute-phase response were determined: C-reactive protein (CRP), alpha2-macroglobulin, haptoglobin, acid alpha1-glycoprotein, prealbumin and albumin. Besides, proinflammatory cytokines (tumor necrosis factor-alpha, IL-6, IL-8) and the anti-inflammatory cytokine IL-10 were also measured. We have found that coronary angioplasty with stent implantation produces a systemic inflammatory response with a rise in inflammation markers concentration. CRP plasma levels declined 1 week after the intervention, but the other marker levels were even higher after 7 days. IL-6 was the only cytokine whose plasma levels significantly increased in peripheral blood after stenting, with a rise after 24 h, maintained after 48 h, and decreased to near-basal levels after 1 week. There was a good correlation between CRP and IL-6 plasma levels (r=0.5, p<0.001). IL-10 levels were slightly decreased after 24 h. Although no significant differences in the means at different time points were found, there was a decrease in IL-10 in most patients 24 h after the intervention. These results indicate that coronary stent implantation induces a systemic inflammatory reaction, with a temporal increase in the concentration of the inflammation markers, especially CRP and IL-6. Since these markers had been previously used as prognostic markers, this needs to be taken into account in patients undergoing stent implantation.
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PMID:Inflammatory response to coronary stent implantation in patients with unstable angina. 1239 2

Biological markers in nasal secretions provide valuable information on nasal pathophysiology. However, published data on biomarker concentrations in nasal fluids are remarkably inconsistent, and the bias due to different sampling techniques, has not yet been systematically evaluated. Concentrations of various protein were repeatedly determined in nasal secretions of 16 healthy volunteers. The proteins were detected by using: 1) alpha2-macroglobulin as a marker for plasma contamination; 2) lactoferrin as a marker for glandular secretion; 3) lactate dehydrogenase as a marker for tissue injury; and 4) interleukin (IL)-1beta, IL-8, tumour necrosis factor-alpha, and eosinophil cationic protein and tryptase as indicators for tissue inflammation. A total of four different sampling methods, including nasal lavage (NL) and a new polyurethane foam sampler technique (PFST) were employed. Analyte concentrations in NL were approximately 10-times lower than in specimens obtained by PFST. Due to the unpredictable dilution during NL, various analytes were below the detection limit of the high sensitivity assays employed. With PFST, concentrations below the detection limit rarely occurred. The specimens did not significantly differ regarding plasma contamination, glandular secretion or tissue injury. The considerable variability of reported analyte concentrations in nasal secretions mainly results from different sampling techniques. To collect nasal secretions, samplers are considered superior to nasal lavage techniques.
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PMID:Biological markers in nasal secretions. 1276 42

The authors examined serum in patients with ovarian cancer (OC; a disseminated process), ovarian cystadenoma (OCA), or external endometriosis (EM) before treatment and in apparently healthy females (a control) for the content of some acute-phase proteins and cytokines to clarify the specific features of changes in their concentrations in relation to the type of the proliferative process. It was shown that in OC, there were significant reductions in the levels of alpha2-macroglobulin (MG), plasmin (PL), alpha1-antitrypsin (AT) and statistically significantly increases in the content of lactoferrin (LF), interleukin (IL)-6, IL-8, Ig, and the regulatory transport complex of P--M. In M, the concentrations of AT were lower and those of IL-6, IL-8, and PL-MG were higher (to a lesser degree than those in OC). In OCA, the levels of MG and IgA were increased; those of IL-8 and PL-MG were decreased. The concentrations of interferon and IgM were unchanged in all groups. The findings suggest that difefrent proliferative processes initially provoke a number of changes of varying magnitude and even directions in the serum levels of inflammation reactants, which should be borne in mind when conducting clinical tests in the intraoperative and, probably, postoperative periods.
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PMID:[Various acute phase reactants in different types of proliferative diseases of the uterine appendages]. 2000 Jan 8

Psoriasis is a chronic, relapsing, inflammatory - proliferative disease, belonging to the group of autoimmune disorders. Although the disease process concerns mainly the skin, this is a systemic inflammation. In psoriasis there is an increased synthesis of proinflammatory proteins, such as: C-reactive protein (CRP), interleukin 1 (IL-1), IL-2, IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), alpha2-macroglobulin, alpha1-antitrypsin and ceruloplasmin. Many studies have shown increased incidence of the metabolic syndrome in patients with psoriasis. There is also relationship between severity of psoriasis and severity of the various components of metabolic syndrome (impaired glucose tolerance or diabetes, abdominal obesity, atherogenic dyslipidemia and hypertension). Chronic inflammation seems to be a link between psoriasis and various components of metabolic syndrome. Proinflammatory cytokines may cause atherosclerosis, insulin resistance, hypertension and type 2 diabetes. Presence of obesity and particular components of the metabolic syndrome may also play an important role in the pathogenesis of chronic kidney disease in patients with psoriasis. The primary intervention in patients with psoriasis and metabolic syndrome in order to reduce cardiovascular risk are lifestyle modifications, i.e. increased physical activity and dietary treatment of obesity, in combination with pharmacotherapy of particular components of metabolic syndrome.
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PMID:[Metabolic disorders in patients with psoriasis]. 2251 79


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