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)

To evaluate the role of granulocyte elastase (GEL) at cardiopulmonary bypass (CPB), the plasma GEL level was measured in 24 patients who underwent elective cardiac surgery and 47 patients who underwent elective gastroenterological surgery. The cardiac surgical patients were divided into two groups: 5 patients with CPB less than 120 minutes (HL group), and 19 patients with CPB more than 120 minutes (HH group). The patients with gastro-enterological surgery were also divided into two groups: 15 patients with postoperative complications (GC group), and 32 patients without postoperative complications (GU group). All the patients of GU, HL and HH groups were alive. Two patients of GC group died because of multiple organ failure (MOF). The serum levels of GEL in both the HH group and the GC group remained higher than in the GU group at 6 postoperative day (POD). The high serum level of IL-8 gave rise to high serum level of GEL in the HH group, even after cardiac surgery. We assumed that anti-cytokine therapy and aggressive administration of Ulinastatin are useful against postoperative complications and that careful management is need after long CPB.
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PMID:[Clinical evaluation of patients with cardiopulmonary bypass by plasma granulocyte elastase]. 759 27

We investigated the inhibitory effects of a protease inhibitor, FUT-175, on the production of interleukin 8 (IL-8) and polymorphonuclear leukocyte elastase (PMNE) by polymorphonuclear leukocytes (PMN) and vascular endothelial cells. IL-8 production by PMN and vascular endothelial cells stimulated with lipopolysaccharide (LPS) was inhibited by FUT-175. This compound also inhibited PMNE production by PMN following LPS stimulation.
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PMID:Inhibitory effect of FUT-175 on the production of interleukin 8 and polymorphonuclear leukocyte elastase. 762 Aug 20

Cystic fibrosis (CF) is characterized by a dramatic neutrophil recruitment and repeated Pseudomonas infections in the lungs. To evaluate cytokine releasibility by airway epithelial cells in the context of CF, we studied primary nasal epithelial cells isolated from the upper airways and continuous epithelial cell lines from normal and CF subjects. Relatively low levels of interleukin (IL)-8, IL-6, and granulocyte/macrophage colony-stimulating factor (GM-CSF) were produced spontaneously by primary epithelial cells (< 50 pg/10(6) cells) and higher levels of colony-stimulating factor-1 (CSF-1) (1 to 2 ng/10(6) cells). Cells were stimulated with substances that are likely to be present in the inflamed lungs of CF patients-namely, the proinflammatory monokines IL-1 and tumor necrosis factor-alpha (TNF alpha) as well as neutrophil elastase and bacterial products from Pseudomonas (mucoid exopolysaccharide [MEP] and rhamnolipids). Both IL-1 and TNF alpha induced a dose-dependent release of IL-6 (5 to 10 ng/10(6) cells) and GM-CSF (2 to 3 ng/10(6) cells) by primary epithelial cells from eight normal volunteers. The TNF alpha/IL-1-stimulated GM-CSF release was blocked by the addition of 1 microM dexamethasone, whereas basal CSF-1 release was unaffected. Neutrophil elastase was a potent inducer of IL-8 and GM-CSF both in primary epithelial cells and in cell lines. Dexamethasone (1 microM) did not inhibit elastase-induced IL-8 release in either normal or CF epithelial cells. Rhamnolipids and MEP were found to stimulate the copious release of IL-8, GM-CSF, and IL-6 from epithelial cells, in a steroid-sensitive fashion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Release of interleukin-8, interleukin-6, and colony-stimulating factors by upper airway epithelial cells: implications for cystic fibrosis. 769 Nov 10

To evaluate the inflammatory response to the cardiopulmonary bypass, we investigated the serum levels of tumor necrosis factor alpha (TNF alpha), interleukin 8 (IL-8), and the expression of leukocyte adhesion molecule CD18. Six patients who underwent elective coronary artery bypass grafting were studied. TNF alpha was elevated significantly 30 minutes after the start of CPB and returned to the baseline 60 minutes after CPB. IL-8 increased significantly after the start of CPB and reached a peak at 10 minutes after release of the aortic cross-clamp, remaining significantly elevated until 10 minutes after the end of CPB (P < 0.05). Circulating neutrophil count and granulocyte elastase increased significantly 10 minutes after release of the aortic-cross clamp and remained high until the first postoperative day. The increase of the neutrophil CD18 expression was not observed. This study demonstrates elevated TNF alpha and IL-8 levels during CPB followed by increases of the neutrophil and the granulocyte elastase, which may be of importance in the systemic inflammatory response to CPB, especially in the development of postperfusion lung injury.
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PMID:[Responses of TNF alpha, IL-8, and leukocyte adhesion molecule CD18 to cardiopulmonary bypass]. 769 21

Whether or not IL-8 attracts T lymphocytes and activates neutrophils in vivo remains unclear. Most studies on function of IL-8 in vivo have been done on human IL-8 in heterologous animals. To elucidate the role of IL-8 in vivo, we injected homologous IL-8 into rabbit knee joints and investigated the inflammatory response. Injection of 10 micrograms of rabbit IL-8 induced a massive accumulation of neutrophils. IL-8 attracts T lymphocytes in vitro; however, rabbit IL-8 induced no appreciable lymphocyte accumulation in rabbits. Although human IL-8 was reported not to induce cartilage destruction when injected into heterologous animals, we observed that rabbit IL-8 did provoke a release of neutrophil elastase, leading to cartilage destruction, when injected into rabbits. An inhibitor against neutrophil elastase (ONO-5046) prevented destruction of the cartilage. Injection of rabbit IL-8 induced bioactive and immunoreactive IL-1 beta and IL-1 receptor antagonist (IL-1Ra) in the joint cavity. Immunohistochemistry showed that IL-1 beta and IL-1Ra positive cells were infiltrating leukocytes. In neutrophil-depleted rabbits, rabbit IL-8 induced far lesser concentrations of IL-1 beta and IL-1Ra and no cartilage destruction compared with findings in normal rabbits. Thus, the infiltrating neutrophils are the main producers of these cytokines and are responsible for the cartilage destruction. In addition to neutrophil chemotactic activity, IL-8 proved to have a neutrophil-activating capability in vivo, with respect to release of neutrophil elastase and induction of IL-1 beta and IL-1Ra.
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PMID:Neutrophil accumulation and activation by homologous IL-8 in rabbits. IL-8 induces destruction of cartilage and production of IL-1 and IL-1 receptor antagonist in vivo. 773 Jun 43

The effects of ulinastatin on the serum interleukin 8 and 6 (IL-8, 6), granulocyte elastase (GEL), creatinphosphokinase (CK) and CK-MB were studied during open heart surgery under cardiopulmonary bypass (CPB). Eleven patients (group I) did not receive ulinastatin. Thirteen patients (group II) received 600,000 units of ulinastatin intravenously before CPB and before declamping of aorta and 12 patients (group III) received 300,000 units more added in the priming solution. The serum concentration of IL-8 and 6 increased at 60, 120, 180 min. after reperfusion compared with the preoperative value in the three groups. But, at each time point after reperfusion, IL-8 and 6 levels in group II and III were significantly lower (P < 0.01) than those in group I. GEL increased progressively after reperfusion in the three groups. There was no significant difference in the three groups with CK-MB as well CK release. These results suggest that ulinastatin is useful for protection of reperfusion injury after myocardial ischemia since ulinastatin suppresses production of IL-8 and 6.
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PMID:[The inhibitory effects of ulinastatin on the increase of interleukin 8 and 6 during open heart surgery]. 783 97

Secretory leukoprotease inhibitor (SLPI), a 12-kD nonglycosylated serine antiprotease, helps to protect the epithelial surface of the airways from the destructive capacity of neutrophil elastase. Based on the recognition that SLPI levels can increase in the presence of airway inflammation, we hypothesized that inflammatory stimuli should modulate the expression of the SLPI gene in airway epithelial cells. To evaluate this, the modulation of SLPI gene expression with various inflammatory stimuli was evaluated in the HS-24 human bronchial epithelial cell line. After preliminary studies showed that several inflammatory mediators enhanced SLPI messenger RNA (mRNA) levels, PMA was used as a model inflammatory stimulus. PMA significantly increased the level of 0.7-kb SLPI mRNA transcripts in HS-24 cells in a dose- and time-dependent fashion and increased the amount of SLPI protein in the culture supernatant. Nuclear run-on analyses showed that the SLPI gene transcription rate increased approximately twofold after PMA stimulation. Transfection studies using fusion genes composed of fragments of up to 1.2 kb of the 5' flanking sequence of the SLPI gene and a luciferase reporter gene demonstrated potent promoter activity in the 131-bp segment (-115 to +16 relative to the transcription start site), and all longer segments up to 1.2 kb, whereas smaller segments showed low promoter activity. An 18-bp element (-98 to -115), in a region with homology to PMA-responsive regions in the Moloney murine leukemia virus enhancer and the IL-8 gene, was shown to be of importance in the level of transcription of the SLPI gene. However, this element was not responsible for the upregulation of SLPI gene expression by PMA. Evaluation of HS-24 cells in the presence of actinomycin D demonstrated that SLPI mRNA transcripts were very stable and became more so in the presence of PMA. Thus, SLPI gene expression in airway epithelial cells can be upregulated by an inflammatory stimulus, and this modulation is regulated at both the transcriptional and posttranscriptional levels. These mechanisms of SLPI upregulation likely play a role in defending the epithelial surface in the local milieu of inflammatory lung diseases.
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PMID:Modulation of secretory leukoprotease inhibitor gene expression in human bronchial epithelial cells by phorbol ester. 791 12

We investigated the mechanisms and consequences of neutrophil accumulation in the airspace in 11 patients with systemic sclerosis (SSc) and interstitial lung disease. Seven normal subjects served as controls. We measured total neutrophil elastase burden, elastase activity, and alpha-1-antitrypsin (alpha 1AT) in bronchoalveolar lavage (BAL) fluid and we evaluated the in vitro interleukin-8 (IL-8, a potent chemoattractant for neutrophils) secretion by alveolar macrophages (AM). A mild neutrophil alveolitis was observed in patients when compared with control subjects. Total BAL elastase burden was higher in patients than in control subjects and correlated positively with the percentage of neutrophils in BAL. BAL elastase activity was undetectable in control subjects, but it was detected in all patients but one (mean: 257 +/- 87 mU/L). Spontaneous IL-8 secretion by AM was higher in patients with SSc than in control subjects (518 +/- 115 versus 228 +/- 65 ng/ml, p = 0.04) and positively correlated with the percentage of neutrophils in BAL (r = 0.505). We conclude that (1) the neutrophil could participate in the pathogenesis of SSC lung disease through the release of elastase; (2) the AM could contribute to the influx of neutrophils in the alveolus through the release of IL-8.
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PMID:Interleukin-8 and neutrophils in systemic sclerosis with lung involvement. 795 65

Chronic airway inflammation is an important feature of cystic fibrosis (CF), markedly influencing morbidity and mortality. We wanted to assess the contribution of the respiratory epithelium in the mediation of local inflammatory events, and, more particularly, its regulating role through cytokine secretion. We have studied the regulation of interleukin-6 and 8 (IL-6 and IL-8) production by the SV40 transformed airway epithelial cell line JME/CF15 (homozygous for the deletion of Phe 508). We show that unstimulated JME/CF15 cells secrete IL-6 and IL-8. Neutrophil chemotactic activity (NCA) is detected in supernatants. The secretion of IL-6 and IL-8 is increased following stimulation of the JME/CF15 cells by IL-1 beta and neutrophil elastase. Lipopolysaccharide and granulocyte macrophage colony stimulating factor (GM-CSF) have no effect on secretion of IL-6 or IL-8. Neutrophil elastase inactivates recombinant human IL-6 at 37 degrees C in vitro, but has no effect at 4 degrees C, suggesting a proteolytic effect of elastase on IL-6. IL-8 activity remains preserved, even after prolonged exposure to elastase. Our data suggest that the airway epithelium may play an active role in the mediation of neutrophil chemotaxis. Local production of IL-8 in response to elastase and IL-1 beta, together with the inactivation of the anti-inflammatory protein IL-6, may result in a significant upregulation of airway inflammation in cystic fibrosis.
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PMID:Regulation of cytokine secretion by cystic fibrosis airway epithelial cells. 811 34

Myocardial ischaemia is one of the major causes of low output syndrome during open heart surgery. Injury associated with ischaemia and reperfusion has been considered to result, in part, from the action of neutrophils, the interaction of neutrophils with vascular endothelial cells, and the effects of cytokines which are mediators that induce and modify reactions between these substances. We investigated cell injury in relation to the concentrations of interleukins 6 and 8 (IL-6 and IL-8), which have recently received attention as neutrophil activators. Neutrophil counts, granulocyte elastase (GEL), IL-6, IL-8, tumour necrosis factor-alpha (TNF-alpha), CK, and CK-MB concentrations were determined serially in 11 patients undergoing open heart surgery with cardiopulmonary bypass (CPB). Neutrophil counts (mean +/- SD 2717 +/- 2421 microliters-1 preoperatively) peaked 60 min after declamping the aorta at 7432 +/- 4357 microliters-1 (P < 0.01) and remained elevated 7136 +/- 5194 microliters-1 at 180 min (P < 0.01). Plasma GEL level (168 +/- 71 micrograms.L-1 preoperatively) peaked at 1134 +/- 453 micrograms.L-1 120 min after declamping of the aorta (P < 0.01) and remained elevated, 1062 +/- 467 micrograms.L-1, after 180 min (P < 0.01). Serum IL-6 level (118 +/- 59 pg.ml-1 preoperatively) peaked at 436 +/- 143 pg.ml-1 60 min after declamping of the aorta (P < 0.01) and remained elevated, 332 +/- 109 pg.ml-1, after 180 min. Serum IL-8 level (37 +/- 44 pg.ml-1 preoperatively) peaked at 169 +/- 86 pg.ml-1 at 60 min after declamping of the aorta (P < 0.001) and remained elevated at 113 +/- 78 pg.ml-1 180 min after declamping of the aorta.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Elevation of cytokines during open heart surgery with cardiopulmonary bypass: participation of interleukin 8 and 6 in reperfusion injury. 826 59


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