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

Connective tissue-activating peptide-III (CTAP-III) is a 9 kd platelet alpha-granule-derived growth factor. It stimulates the synthesis of DNA, hyaluronic acid, glycosaminoglycans, and proteoglycan core protein in human fibroblasts. Human mononuclear cell-derived proteases have been previously demonstrated to digest the N-terminal 15 residues of CTAP-III (total, 85 residues) to produce neutrophil-activating peptide-2 (NAP-2). CTAP-III and NAP-2 belong to a class of proteins (platelet factor 4, interleukin-8/NAP-1, etc.) associated with inflammation and wound repair. In our efforts to purify human mononuclear cells and platelet-derived histamine-releasing factors, we had previously discovered that mixtures of CTAP-III and NAP-2 released histamine from human basophils. We have now developed simple protocols for the purification of CTAP-III and NAP-2, independently, from calcium ionophore (A23187)-stimulated platelet supernatants by affinity chromatography and have established their identity by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and N-terminal sequence analysis. Each of these related histamine between 2 and 10 micrograms/ml, a range identical to that obtained with CTAP-III/NAP-2 mixtures that we reported earlier. Thus, our data suggest that CTAP-III and NAP-2 independently release histamine from human basophils in dose ranges similar to ranges required for fibroblast stimulation by each.
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PMID:Connective tissue-activating peptide-III and its derivative, neutrophil-activating peptide-2, release histamine from human basophils. 137 16

Connective tissue activating peptide-III (CTAP-III) is a component of platelet alpha-granules which elicits a series of responses in connective tissue cells referred to as activation, including increased glucose consumption and mitogenesis and increased secretion of hyaluronic acid and glycosaminoglycans. As anticipated by a requirement for glucose or glucose precursors in the activation process, an early event following CTAP-III activation of connective tissue cells is an increase in glucose transport. The present study investigates the molecular basis for this increase in glucose transport. Murine 3T3-F442A fibroblasts were found to respond to CTAP-III in a manner similar to human connective tissue cells (synovial cells, chondrocytes, skin fibroblasts). CTAP-III increases the rate of glucose transport to similar extents at 4 and 24 h, and at physiologic (micrograms/ml) concentrations of CTAP-III. A proteolytic cleavage product of recombinant CTAP-III (rCTAP-III-Leu-21 (des-1-15)), also known as neutrophil-activating peptide-2 (NAP-2), was found to be equally effective as CTAP-III, whereas NAP-1/interleukin-8, another member of the CTAP-III super-family, was ineffective in stimulating glucose transport. This contrasts with neutrophil chemotaxis, in which CTAP-III (des-1-15)/NAP-2 acts similarly to NAP-1/interleukin 8 while CTAP-III is ineffective. CTAP-III appears to elicit a different type of glucose transport response than many other growth factors in that its response is sustained (greater than or equal to 24 h) rather than transient (peak approximately 4 h) in confluent as well as in subconfluent cells. Western blot analysis using antibodies to the GLUT-1 glucose transporter revealed an increased level of GLUT-1 protein in response to CTAP-III isoforms that corresponded in magnitude (on a percentage basis) to the increased level of glucose transport. The increased levels of GLUT-1 protein in response to CTAP-III and rCTAP-III-Leu-21 (des-1-15)/NAP-2 were accompanied by an increase in levels of GLUT-1 mRNA of a magnitude sufficient to account for observed increased levels of GLUT-1. These results are consistent with CTAP-III isoforms stimulating glucose transport in connective tissue cells by increasing levels of GLUT-1 mRNA and is one of the few known instances in which increases in levels of GLUT-1 mRNA and protein are sufficient to account for observed increases in glucose transport. They also provide further evidence that CTAP-III (des-1-15)/NAP-2 binds to more than one type of receptor and that CTAP-III acts in a manner different than other well characterized growth factors (e.g. platelet-derived growth factor, transforming growth factor-beta) in that it causes a sustained (greater than or equal to 24 h) elevation in glucose transport in confluent as well as subconfluent cells.
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PMID:Regulation of glucose transporters by connective tissue activating peptide-III isoforms. 152 75

Angiogenesis in vivo is distinguished by four stages: subsequent to the transduction of signals to differentiate, stage 1 is defined as an altered proteolytic balance of the cell allowing it to digest through the surrounding matrix. These committed cells then proliferate (stage 2), and migrate (stage 3) to form aligned cords of cells. The final stage is the development of vessel patency (stage 4), generated by a coalescing of intracellular vacuoles. Subsequently, these structures anastamose and the initial flow of blood through the new vessel completes the process. We present and discuss how the available models most closely represent phases of in vivo angiogenesis. The enhancement of angiogenesis by hyaluronic acid fragments, transforming growth factor beta, tumor necrosis factor alpha, angiogenin, okadaic acid, fibroblast growth factor, interleukin 8, vascular endothelial growth factor, haptoglobin, and gangliosides, and the inhibition of the process by hyaluronic acid, estrogen metabolites, genestein, heparin, cyclosporin A, placental RNase inhibitor, steroids, collagen synthesis inhibitors, thrombospondin, fumagellin, and protamine are also discussed.
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PMID:Angiogenesis: models and modulators. 753 24

We report that polyethylene particles can activate mononuclear cells within the joint to produce the monocyte chemotactic and activating factor (MCAF) and to a lesser degree interleukin 8 (IL-8) as judged by immunohistological staining. Polyethylene particles suspended in hyaluronic acid were injected weekly for 12 weeks into the right knee joint of New Zealand white rabbits. The average size of the particles was 7 (3-12) microns in diameter. The left knee joint was injected with hyaluronic acid as the control. The animals were killed after 13 weeks. On the control side, the synovial membrane was histologically normal, without signs of inflammation. In the knees that were injected with polyethylene particles, histological analysis showed a weak inflammatory response, consisting of mononuclear cells, multi-nucleated giant cells and polyethylene particles. In the vicinity of the particles, the presence of mononuclear cells that were highly positive for MCAF was noted, whereas IL-8 was present in endothelial cells and in the lining layer, but not in cells in the vicinity of polyethylene particles, suggesting that polyethylene particles are able to activate cytokine metabolism in a differentiated way in the synovial monocytes.
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PMID:Polyethylene particles stimulate monocyte chemotactic and activating factor production in synovial mononuclear cells in vivo. An immunohistochemical study in rabbits. 862 84

Poor initial graft function may increase postoperative morbidity including the risk of early allograft rejection. Various mediators, including immunostimulatory cytokines, may be released during reperfusion in relation to the extent of preservation and reperfusion injury. For this purpose, 81 patients with 85 liver transplants were monitored for cytokines, adhesion molecules, extracellular matrix (ECM) parameters, and neopterin at predefined time-points during and after transplantation. To estimate the origin of cytokine release, blood was obtained central and hepatic venously for the first 48 hr after reperfusion and subsequently from a peripheral vein. One-year patient survival was 88.9%; no relation to initial graft function was observed. Poor initial graft function failed to increase the risk for subsequent infectious complications but was associated with an increased risk of early allograft rejection. The incidence of steroid-resistant rejection was significantly increased in patients with poor initial graft function (35.7% versus 12.7% in patients with good and moderate initial graft function; P < or = 0.05). Various cytokines, adhesion molecules, and ECM parameters including sTNF-RII, sIL-2R, IL-8, IL-10, sVCAM-1, E-selectin, hyaluronic acid, sialic acid, and laminin correlated significantly with the extent of preservation and reperfusion injury. Although none of these parameters was more appropriate in determining the extent of preservation and reperfusion injury than currently established parameters (AST, ALT, and color and amount of bile production), the combined increase in these parameters may not only promote tissue repair but may also perpetuate liver allograft injury and thereby cause significant morbidity. Besides cytokines and adhesion molecules, the ECM may play a pivotal role in determining repair or ongoing tissue injury. Ongoing changes at the microvasculature and basement membrane may result in an increase of local and circulating cytokines and adhesion molecules, which increase the risk of subsequent early allograft rejection. Furthermore, the increase in sTNF-RII, E-selectin, and laminin during reperfusion was predictive of subsequent development of acute allograft rejection. These observations may be of value for further strategies to decrease reperfusion injury and prevent early allograft rejection.
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PMID:The release of cytokines, adhesion molecules, and extracellular matrix parameters during and after reperfusion in human liver transplantation. 890 Mar 13

During pregnancy, hyaluronic acid (HA) concentration in the human cervix is very low, but increases rapidly at the onset of labour. HA has a high affinity for water molecules and hence can maintain tissue hydration. HA can stimulate collagenase production in rabbit cervix, and also stimulates migration and function of polymorphonuclear leukocytes in the tissues. It is an endogenous regulator of interleukin-1 (IL-1). We hypothesized that HA plays an essential role during cervical ripening. The effect of exogenous application of HA (20 mg) on non-pregnant and pregnant (day 23) rabbit cervices was compared with controls. HA induced cervical ripening in both pregnant and non-pregnant animals, and cervical water content was significantly increased. Tissue collagen was markedly decreased. The localization and distribution of HA and HA receptor CD44 was determined in non-pregnant and pregnant human cervical connective tissue using biotinylated HA binding protein and CD44 monoclonal antibodies. Both were widely distributed in the connective tissues, especially around the blood vessels and cervical glands. The effect of IL-8 (50, 100, 150 and 200 ng/ml) on HA production and hyaluronidase (HAase) activity was investigated in cultures of lower uterine segment collected during elective Caesarean sections. HA production was stimulated in a dose-dependent manner; there was no effect on hyaluronidase activity. HA administration (0.5, 1 and 2 mg/ml) stimulated the activities of collagenase and gelatinase together with IL-8 production in the culture supernatants. Thus HA may play an important role in cervical ripening, being involved in the regulation of cervical tissue water content, collagenolytic enzymes and cytokines.
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PMID:The role of hyaluronic acid as a mediator and regulator of cervical ripening. 919 70

To clarify the mechanism of hyperbilirubinemia in the setting of a left ventricular assist device (LVAD), the change in hepatocellular function, hepatic sinusoid endothelial microcirculation, and inflammatory response before and after LVAD implantation were evaluated. Eight consecutive patients underwent the placement of an LVAD, and serum levels of total bilirubin (TB), transaminases [alanine transaminase (ALT), aspartate transaminase (AST)], interleukin (IL-6, IL-8), and hyaluronic acid (HA), an indicator of hepatic sinusoidal circulation, were measured before and after LVAD implantation. The TB of all patients increased significantly in the first post operative week (p < 0.05 vs. pre-operatively). In five patients, the elevated TB (4.6 +/- 4.1 mg/dl) returned to pre-operative levels (2.7 +/- 2.0 mg/dl) by the 14th post operative day (Group R), but in the other three patients who died of multiple organ failure, the level of TB increased to 39.9 +/- 16.4 mg/dl (Group A). Levels of HA and IL-8 had good correlation with the level of TB (HA: r = 0.60, p < 0.05; IL-8: r = 0.55, p < 0.05). However, AST, ALT, and IL-6 were not related to changes in TB. These results suggest that hepatic sinusoid endothelial dysfunction and inflammatory reaction may play a significant role in hepatic failure in patients following implantation of an LVAD.
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PMID:Hepatic sinusoid endothelial dysfunction plays a role in hyperbilirubinemia in patients following implantation of an LVAD. 936 82

Cold preservation/reperfusion leads to sinusoidal endothelial cell (SEC) activation and damage in nearly every liver transplantation; the extent of these changes influences early graft function. Upon reperfusion, activated SEC show increased expression of adhesion molecules, including von Willebrand factor (vWF) which is released into the circulation. This study was designed to evaluate the levels of vWF measured in the caval effluent and correlate these findings with known markers of SEC damage and early graft function. Data were obtained from 35 patients undergoing orthotopic liver transplantation (LTx). Two samples were taken from each patient for measurement of vWF: a) from the portal vein immediately prior to reperfusion; and b) from the first 50 ml of the caval effluent. Commercial assays were used to measure vWF, as well as hyaluronic acid (HA), thrombomodulin (TM), IL-1 beta, IL-6, IL-8 and TNF-alpha. Patients were divided into two groups based on early graft function. Poor early graft function (PEGF) was defined as a peak aspartate transaminase (AST) or alanine transaminase (ALT) level > 2500 U/L during the first three postoperative days (POD) and a prothrombin time (PT) > 16 s on POD 2 (n = 8). The remaining 27 patients had good early graft function (GEGF). In patients with GEGF, vWF levels dropped significantly between the two time points. This change was not observed in those with PEGF. A positive linear correlation was observed in the PEGF group between vWF and HA and IL-6. The different pattern of change in vWF between the two groups, as well as the positive correlation between HA, IL-6 and vWF in PEGF, suggest that vWF may be a useful marker of early graft function.
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PMID:Correlation between von Willebrand factor levels and early graft function in clinical liver transplantation. 1008 31

The purpose of this research was to study the changes in the molecular weight of hyaluronic acid in Wharton's jelly altered by necrotizing funisitis. Umbilical cords were collected at delivery from 20 newborns without funisitis, 6 newborns with acute funisitis, and 4 newborns with necrotizing funisitis. Agarose gel electrophoresis of Wharton's jelly was performed to analyze the molecular weight of hyaluronic acid (HA). We also investigated the effects of low or high molecular weight HA on the production of interleukin-8 in human umbilical fibroblasts. In Wharton's jelly without funisitis, HA was 1150 +/- 280 kD in preterm newborns, regardless of gestational week at birth, and that in full-term newborns was 1100 +/- 200 kD. When acute funisitis was present, HA was 700 +/- 250 kD, and when necrotizing funisitis was present, HA was 520 +/- 100 kD. The molecular weight of HA was significantly below normal in newborns with necrotizing funisitis. Low molecular weight HA was associated with increased levels of IL-8 in the supernatant of cultured human umbilical fibroblasts in a time- and dose-dependent manner. High molecular weight HA did not induce the production of IL-8 in the same cells. Low molecular weight HA has a potent inflammatory action. The conversion from high to low molecular weight HA in Wharton's jelly may be important in the pathophysiology of necrotizing funisitis.
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PMID:The role of low molecular weight hyaluronic acid contained in Wharton's jelly in necrotizing funisitis. 1020 42

Hyaluronic acid (HA) stimulates the synthesis of interleukin (IL) 8, while dehydroepiandrosterone sulphate (DHEA-S) induces the expression of IL-8 and its receptor in the human cervical fibroblast. This has led us to investigate the effect of DHEA-S on HA-induced cervical ripening. Experiments were performed in pregnant rabbits using vaginal suppositories containing 1 mg HA, 30 mg DHEA-S, 30 mg DHEA-S + 0.1 mg HA, 30 mg DHEA-S + 1 mg HA, and 500 microl Witepsol-50 base (control). The effects were evaluated by measuring collagenase, gelatinase and elastase activities, water content, neutrophil infiltration, relative collagen concentration and histological assessment. The activities of collagenase, gelatinase and elastase were significantly increased in rabbits treated with DHEA-S + 1 mg HA compared with rabbits treated with DHEA-S + 0.1 mg HA (P < 0.009, P < 0.001, P < 0.009 respectively). Water content was markedly increased in rabbits treated with DHEA-S + 1 mg HA compared with DHEA-S + 0.1 mg HA treatment (P < 0.05). Neutrophil infiltration was markedly increased, while relative collagen concentration was significantly decreased with DHEA-S + 1 mg HA compared with the DHEA-S + 0.1 mg HA approach (P < 0.001, P < 0.002). The histology of cervices treated with DHEA-S + 1 mg HA showed the density of collagen to be markedly decreased, and collagen fibres irregularly separated. Increased vascularity with massive dilatation of blood vessels was also observed in these rabbits. We conclude that DHEA-S upregulates the HA-induced cervical ripening process.
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PMID:Dehydroepiandrosterone sulphate promotes hyaluronic acid-induced cervical ripening in rabbits. 1032 94


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