UNIPROT:P10145 - FACTA Search

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Query: UNIPROT:P10145 (IL-8)
23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fluoride has been in focus as a possible causal agent for respiratory symptoms amongst aluminium potroom workers for several decades. Previously, using bronchoalveolar lavage (BAL), we demonstrated airway inflammation in healthy volunteers 24 hours after exposure to hydrogen fluoride (HF). The objective of the present study was to examine early lung responses to HF exposure. Bronchoscopy with BAL was performed 2 hours after the end of 1-hour exposure to HE Significant reductions in the total cell number and the number of neutrophils and lymphocytes were observed in bronchoalveolar portion (BAP), whereas there were no significant changes in the bronchial portion (BP). Significantly decreased concentrations of beta2-MG, IL-6 and total protein were found in both BAP and BP. Additionally, IL-8 was significantly reduced in BP, and ICAM-1 and albumin were present in lower concentrations in BAP. Lung function measurements were not affected by HF exposure. These reported effects are presumably transitory, as many were not present in the airways 24 hours after a similar HF exposure.
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PMID:Inflammatory markers in bronchoalveolar lavage fluid from human volunteers 2 hours after hydrogen fluoride exposure. 1590 Oct 49

Our retrospective analysis of 105 patients with alcoholic liver injury confirmed that patients with severe alcoholic hepatitis (SAH) showed severe hyperbilirubinemia, reduced hepatic biosynthetic capacity, and marked acute inflammatory reactions, and developed multiple organ failure (MOF). Multivariate analysis using the Cox proportional hazards model showed serum C-reactive protein and DIC as significant independent prognostic factors among SAH, LC+AH, and AH groups. Improved assay showed an increase of plasma endotoxin with the progression of alcoholic liver injury. In most survivors, plasma Et levels decreased in the recovery phase. Serum interleukin (IL)-6 and IL-8 levels in the acute phase were high in patients with AH and LC+AH, especially in non-survivors and in patients with SAH. In the recovery phase, these cytokine levels in survivors tended to decrease, but in non-survivors, IL-6 remained high, and IL-8 further increased. Serum levels of HDL and albumin, which are protective against endotoxicity by inhibiting endotoxin uptake and TNF production by macrophages, were decreased with the progression of alcoholic liver injury. Animal experiments supported that the increase in endotoxin-binding capacity of HDL and albumin may serve as a protective mechanism against endotoxin in chronic ethanol-loaded rats and that an addition of high-dose ethanol to these rats may lead to impaired binding and inactivation of endotoxin. Lipopolysaccharide-binding protein (LBP) which enhances endotoxin uptake and TNF production by macrophages, was generally increased in patients with alcoholic liver injury. This imbalance among endotoxin binding proteins in the blood may induce overproduction of cytokines by macrophages in patients with severe alcoholic liver injury. Our animal experiments further revealed that an additional administration of a high-dose ethanol to chronic alcohol-fed rats led to decrease of endotoxin clearance, increased extrahepatic accumulation of endotoxin and elevation of plasma TNF. The splenic macrophages and pulmonary alveolar macrophages are demonstrated to be important for endotoxin uptake, and excessive production of TNF in rats given large amounts of alcohol. An in vitro culture experiment in the presence of rat LBP suggested a role of these macrophages in excessive production of TNF-alpha. When the functions of various macrophages were compared in rats given alcohol, maximum TNF-alpha secretion was noted in alveolar macrophages, In conclusion, endotoxemia and its effects on extrahepatic macrophages may play key roles in the progression of severe alcoholic liver injury and MOF.
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PMID:Relation of endotoxin, endotoxin binding proteins and macrophages to severe alcoholic liver injury and multiple organ failure. 1634 5

To gain insight in the pathogenesis of increased vascular permeability during sepsis, we studied the effect of plasma obtained during human experimental endotoxemia on the permeability of cultured endothelial monolayers. Eight healthy subjects received an i.v. dose of 2 ng/kg Escherichia coli O:113 lipopolysaccharide (LPS). The concentration of various plasma mediators that supposedly induce vascular permeability was measured over time. Plasmas that were obtained before, and 2 and 4 h after the administration of LPS were added to human umbilical venular endothelial cells that were cultured on semipermeable membranes.The permeability of the endothelial monolayers to fluorescein isothiocyanate-labeled bovine serum albumin was determined and expressed as the relative concentration of fluorescein isothiocyanate-bovine serum albumin when compared with that measured across empty Transwell-COL (Corning Life Sciences B.V., Schiphol-Rijk, The Netherlands) membranes (i.e., without endothelial monolayers). The permeability levels were correlated with the concentrations of various mediators.Experimental endotoxemia resulted in elevated levels of tumor necrosis factor alpha, interleukin (IL) 1beta, IL-6, IL-8, IL-10, and vascular endothelial growth factor and a moderate increase of IL-12 and IFN-gamma (all P values < 0.01). Incubation of human umbilical venular endothelial cells with plasma obtained 2 and 4 h after the administration of LPS increased the relative permeability from a baseline level (median) of 17% (range, 14% - 31%) to 23% (range, 12% - 39%; P = not significant) and 28% (range, 11% - 40%; P < 0.05), respectively. Plasma levels of vascular endothelial growth factor and IL-10, but not TNF-alpha or any other mediators, significantly correlated with the increase in endothelial permeability (r = 0.47, P = 0.038; r = 0.43, P = 0.038, respectively). The data presented here demonstrate that plasmas obtained from experimental human endotoxemia increase endothelial albumin permeability in vitro. Thus, cultured human endothelial monolayers provide a model to study sepsis-associated vascular changes.
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PMID:Plasma obtained during human endotoxemia increases endothelial albumin permeability in vitro. 1667 Jun 37

The effects of advanced glycation end products (AGE) in the form of glycated albumin (GA) on the proinflammatory phenotype of cultured renal proximal tubular epithelial cells (PTEC) and the therapeutic potential of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist were studied. Human PTEC were exposed to medium alone or supplemented with albumin or GA with or without previous addition of rosiglitazone (0.1 to 0.5 microM). Exposure to GA (up to 0.5 mg/ml) but not the equivalent dose of neat albumin significantly upregulated both mRNA and protein expression of IL-8 and soluble intercellular adhesion molecule-1 (sICAM-1) in a dose- and time-dependent manner. Using immunohistochemistry, ICAM-1 signals were detected in the tubular epithelia and peritubular capillaries in association with AGE deposition and leukocyte infiltration, whereas IL-8 staining was localized in the tubular epithelia of human diabetic kidney biopsies. Also in a dose-dependent manner, GA (0.5 mg/ml) but not albumin caused nuclear translocation of NF-kappaB and activation of mitogen-activated protein kinase (MAPK) p44/p42 and signal transducer and activator of transcription (STAT-1). Inhibition of these pathways with pyrrolidine dithiocarbamate, PD 98059, and fludarabine, respectively, attenuated GA-induced IL-8 secretion. Rosiglitazone dose-dependently attenuated GA-induced IL-8 and ICAM-1 signals in PTEC and completely abolished GA-induced STAT-1 signals but had no effect on NF-kappaB and MAPK activation. These findings suggest that AGE stimulate renal tubular expression of adhesion molecule and chemokine that together may account for the transmigration of inflammatory cells into the interstitial space during diabetic tubulopathy. Such proinflammatory phenotype may be partially modified by PPAR-gamma ligation through STAT-1 inhibition independent of NF-kappaB transcriptional activity and MAPK signaling.
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PMID:Activation of tubular epithelial cells in diabetic nephropathy and the role of the peroxisome proliferator-activated receptor-gamma agonist. 1668 27

Endothelial cells play an important role in inflammatory disorders, as they control the recruitment of leukocytes into inflamed tissue and the formation of new blood vessels. Activation of p38MAP kinase results in the production of proinflammatory cytokines and the expression of adhesion molecules. P38MAP kinase inhibitors are therefore considered important candidates for the treatment of inflammatory disorders. In the present study, we propose a novel strategy to counteract these processes by delivery of the p38MAP kinase inhibitor SB202190 into angiogenic endothelial cells. A drug-targeting conjugate was developed by conjugation of SB202190 to human serum albumin (HSA) using a novel platinum-based linker. Specificity for angiogenic endothelial cells was introduced by conjugation of cyclic RGD-peptides via bifunctional polyethylene glycol linkers. The final products contained an average of nine SB202190 and six RGDPEG groups per albumin. The platinum-based linker displayed high stability in buffers and culture medium, but released SB202190 slowly upon competition with sulfur-containing ligands like glutathione. RGDPEG-SB-HSA bound to alpha(v3)-integrin expressing endothelial cells (human umbilical cord vein endothelial cells) with low nanomolar affinity and was subsequently internalized. When HUVEC were treated with TNF to induce inflammatory events, pretreatment with RGDPEG-SB-HSA partially inhibited proinflammatory gene expression (IL-8, E-selectin; 30% inhibition) and secretion of cytokines (IL-8, 34% inhibition). We conclude that the developed RGDPEG-SB-HSA conjugates provide a novel means to counteract inflammation disorders such as rheumatoid arthritis.
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PMID:Delivery of the p38 MAPkinase inhibitor SB202190 to angiogenic endothelial cells: development of novel RGD-equipped and PEGylated drug-albumin conjugates using platinum(II)-based drug linker technology. 1698 35

Asthma and chronic obstructive pulmonary disease (COPD) are characterized by chronic airway inflammation and major structural lung tissue changes including increased extracellular matrix (ECM) deposition. Inhaled corticosteroids and long-acting beta(2)-agonists (LABA) are the basic treatment for both diseases, but their effect on airway remodeling remains unclear. In this study, we investigated the effect of corticosteroids and LABA, alone or in combination, on total ECM and collagen deposition, gene expression, cell proliferation, and IL-6, IL-8, and TGF-beta(1) levels by primary human lung fibroblasts. In our model, fibroblasts in 0.3% albumin represented a non-inflammatory condition and stimulation with 5% FCS and/or TGF-beta(1) mimicked an inflammatory environment with activation of tissue repair. FCS (5%) increased total ECM, collagen deposition, cell proliferation, and IL-6, IL-8, and TGF-beta(1) levels. In 0.3% albumin, corticosteroids reduced total ECM and collagen deposition, involving the glucocorticoid receptor (GR) and downregulation of collagen, heat shock protein 47 (Hsp47), and Fli1 mRNA expression. In 5% FCS, corticosteroids increased ECM deposition, involving upregulation of COL4A1 and CTGF mRNA expression. LABA reduced total ECM and collagen deposition under all conditions partly via the beta(2)-adrenergic receptor. In combination, the drugs had an additive effect in the presence or absence of TGF-beta(1) further decreasing ECM deposition in 0.3% albumin whereas counteracting each other in 5% FCS. These data suggest that the effect of corticosteroids, but not of LABA, on ECM deposition by fibroblasts is altered by serum. These findings imply that as soon as airway inflammation is resolved, long-term treatment with combined drugs may beneficially reduce pathological tissue remodeling.
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PMID:Opposite effect of corticosteroids and long-acting beta(2)-agonists on serum- and TGF-beta(1)-induced extracellular matrix deposition by primary human lung fibroblasts. 1701 7

The oxidation theory proposes that LDL oxidation is an early event in atherosclerosis and that oxidized LDL contributes to atherogenesis in triggering inflammation. In contrast to the copper-modified LDL, there are few studies using myeloperoxidase-modified LDL (Mox-LDL) as an inflammation inducer. Our aim is to test whether Mox-LDL could constitute a specific inducer of the inflammatory response. Albumin, which is the most abundant protein in plasma and which is present to an identical concentration of LDL in the intima, was used for comparison. The secretion of IL-8 by endothelial cells (Ea.hy926) and TNF-alpha by monocytes (THP-1) was measured in the cell medium after exposure of these cells to native LDL, native albumin, Mox-LDL, or Mox-albumin. We observed that Mox-LDL induced a 1.5- and 2-fold increase (ANOVA; P < 0.001) in IL-8 production at 100 microg/mL and 200 microg/mL, respectively. The incubation of THP-1 cells with Mox-LDL (100 microg/mL) increased the production of TNF-alpha 2-fold over the control. Native LDL, albumin, and Mox-albumin showed no effect in either cellular types. The myeloperoxidase-modified LDL increase in cytokine release by endothelial and monocyte cells and by firing both local and systemic inflammation could induce atherogenesis and its development.
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PMID:Triggering of inflammatory response by myeloperoxidase-oxidized LDL. 1716 45

Cytokines play a important role in life-threatening liver insufficiency. They are released within the liver in response to hepatic injury and inflammation. To study cytokine clearance during albumin dialysis treatment (Molecular Adsorbent Recirculating System [MARS]), we monitored proinflammatory (tumor necrosis factor alpha [TNF-alpha] and interleukin-8 [IL-8]) and anti-inflammatory (IL-10 and IL-6) cytokines and the lymphocyte activation marker IL-2sRalpha in 81 consecutive ICU patients displaying serious hepatic decompensation. Cytokine levels were measured before treatment and after the last MARS treatment in 49 acute liver failure (ALF) and 32 acute decompensation of chronic liver disease (AcOChr) patients who were mainly considered for liver transplantation. No significant change in cytokines was observed before versus after the last MARS treatment in the AcOChr group, and only IL-10 decreased significantly in the ALF group. Baseline levels of IL-8 and IL-6 were significantly lower and IL-10 was higher in the ALF group compared with those in the AcOChr group. TNF-alpha and IL-2sRalpha levels did not differ between the groups. After treatment, IL-8 was also significantly lower in ALF patients compared with the levels in AcOChr patients. In this study, MARS therapy did not show a clearly identifiable efficacy at removing circulating cytokines. However, the results revealed that ALF and AcOChr patients displayed different profiles of circulating cytokines.
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PMID:Albumin dialysis has no clear effect on cytokine levels in patients with life-threatening liver insufficiency. 1717 26

Cytokines are mediators of the inflammatory response, secreted by many tissues, including adipocytes. Chronic alcoholic liver disease and alcoholic hepatitis are associated with elevated serum cytokine levels which yield prognostic value in this situation. Most studies have been performed in patients with acute alcoholic hepatitis. However, cytokine alterations in stable alcoholics have been less studied, as is also the case for the relationship between cytokines and fat and lean mass in these patients. The aim of the present study was to analyse the relationships between some proinflammatory serum cytokine levels and lean mass, fat mass, nutritional status, and liver function parameters in stable alcoholic patients. We determined serum TNF-alpha, interleukin (IL)-6, IL-8 and TNF receptor 2 (TNFr2) in 77 male alcoholic patients in a stable phase (before hospital discharge). In all patients we performed a total-body composition analysis (Hologic DEXA), nutritional assessment including body mass index, triceps skinfold, brachial perimeter, and assessment of liver function. Forty-two healthy volunteer health workers served as controls. IL-8, TNF-alpha and TNFr2 were significantly higher in patients than in controls. No differences were observed between patients and controls regarding fat mass, but alcoholics showed significantly decreased lean mass than controls. Only IL-6 was significantly related with body fat in patients with elevated IL-6 levels. Poor relationships were observed between lean mass and cytokines; some nutritional parameters showed inverse relationships with serum TNF, whereas TNF and IL-8 were inversely related with albumin and prothrombin activity. Thus, cytokine levels were elevated in stable alcoholic patients, and IL-6 levels showed significant correlation with body fat mass, raising the possibility that adipose tissue contributes to the persistence of high levels of cytokines in stable alcoholics.
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PMID:Pro-inflammatory cytokines in stable chronic alcoholics: relationship with fat and lean mass. 1721 Feb 15

Cytokine-induced inflammation is involved in the pathogenesis of type 2 diabetes mellitus (DM). We investigated plasma concentrations and ex vivo production of cytokines and chemokines, and intracellular signalling molecules, mitogen-activated protein kinases (MAPK) in T helper (Th) cells and monocytes in 94 type 2 diabetic patients with or without nephropathy and 20 healthy controls. Plasma concentrations of inflammatory cytokines tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-18 and chemokine CCL2 in patients with diabetic nephropathy (DN) were significantly higher than control subjects, while IL-10, CXCL8, CXCL9, CXCL10 and adiponectin concentrations of DN were significantly higher than patients without diabetic nephropathy (NDN) and control subjects (all P < 0.05). Plasma concentrations of TNF-alpha, IL-6, IL-10, IL-18, CCL2, CXCL8, CXCL9, CXCL10 and adiponectin exhibited significant positive correlation with urine albumin : creatinine ratio in DN patients. The percentage increases of ex vivo production of IL-6, CXCL8, CXCL10, CCL2 and CCL5 upon TNF-alpha activation were significantly higher in both NDN and DN patients than controls (all P < 0.05). The percentage increases in IL-18-induced phosphorylation of extracellular signal-regulated kinase (ERK) in Th cells of NDN and DN were significantly higher than controls (P < 0.05), while the percentage increase in TNF-alpha-induced phosphorylation of p38 MAPK in monocytes and IL-18-induced phosphorylation of p38 MAPK in Th cells and monocytes were significantly higher in NDN patients than controls. These results confirmed that the aberrant production of inflammatory cytokines and chemokines and differential activation of MAPK in different leucocytes are the underlying immunopathological mechanisms of type 2 DM patients with DN.
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PMID:Aberrant activation profile of cytokines and mitogen-activated protein kinases in type 2 diabetic patients with nephropathy. 1742 53

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