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)

The neutrophil-dominated inflammation of the lung in cystic fibrosis (CF) has traditionally been seen as a physiological response to continuous opportunistic infection. Recent studies suggest, however, that regulation of the inflammatory response itself may be altered in CF. Neutrophil migration from the bloodstream involves alterations in surface expression of the adhesion molecules L-selectin and Mac-1 (CD11b/CD18). The aim of this study was to assess neutrophil adhesion molecule expression and responsiveness in CF. Neutrophils from chronic (n = 16) and acutely infected (n = 13) CF patients and 15 normal control subjects were directly assessed by Fluorescence-activated cell sorter (FACS) analysis for surface expression of L-selectin and CD11b before and after stimulation with interleukin 8 (IL-8) or f-Met-Leu-Phe (fMLP). Neutrophils from stable (n = 5) and acutely infected (n = 5) non-CF bronchiectasis patients were also assessed. Surface upregulation of CD11b was similar in all groups. Basal levels of L-selectin were also comparable among all groups, however, when stimulated, neutrophils from both stable and acutely infected CF patients shed significantly less L-selectin than those from control subjects (p < 0.05 and p < 0.01, respectively). This decreased responsiveness was not observed in either stable or acutely infected non-CF bronchiectasis patients. These results add to the accumulating evidence suggestive of a defective inflammatory response in CF.
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PMID:Neutrophil adhesion molecule surface expression and responsiveness in cystic fibrosis. 951 87

Stimulation of human neutrophils with inflammatory mediators such as TNF-alpha or platelet-activating factor (PAF) induces translocation of adhesion molecule Mac-1 (CD11b/CD18) from secretory vesicles to the plasma membrane. Type II phospholipase A2 (PLA2-II) also induces translocation of Mac-1 from secretory vesicles. However, there are more Mac-1 molecules in gelatinase granules and specific granules than in secretory vesicles. Therefore, different combinations of PLA2-II and other mediators were examined for their ability to induce gelatinase granules and specific granules to induce Mac-1 surface expression. The combination of PLA2-II and PAF synergistically increased Mac-1 surface expression, and the effect was greater than the combinations of PLA2-II with TNF-alpha, IL-8, or FMLP. Additionally, the combination of PLA2-II and PAF induced exocytosis of both secretory vesicles and gelatinase granules, which did not occur with either PLA2-II alone or PAF alone. The induction was accompanied by marked production of leukotriene B4. AA861, an inhibitor of 5-lipoxygenase, did not inhibit exocytosis of secretory vesicles but did inhibit exocytosis of gelatinase granules and decrease Mac-1 surface expression. It was also found that Ca2+ influx is essential for 5-lipoxygenase activation, because Ni2+, which blocks the influx of extracellular Ca2+, inhibited the production of leukotriene B4. These results suggest that stimulation by the combination of PLA2-II and PAF, unlike stimulation by each mediator alone, causes exocytosis of gelatinase granules via the 5-lipoxygenase pathway, resulting in a synergistic increase in neutrophil Mac-1 surface expression during inflammatory processes.
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PMID:Synergistic effect of type II phospholipase A2 and platelet-activating factor on Mac-1 surface expression and exocytosis of gelatinase granules in human neutrophils: evidence for the 5-lipoxygenase-dependent mechanism. 959 Feb 57

We examined the effect of the neutrophil chemoattractants interleukin (IL)-8 and N-formyl-methionyl-leucyl-phenylalanine on goblet cell (GC) degranulation in guinea pigs. Chemoattractants caused time-dependent neutrophil recruitment and GC degranulation in vivo. NPC 15669 (an inhibitor of leukocyte infiltration) prevented both responses, implicating neutrophils. ICI 200,355 (an inhibitor of neutrophil elastase and proteinase-3) or secretory leukocyte protease inhibitor (an inhibitor of elastase but not of proteinase-3) abolished IL-8-induced GC degranulation, implicating elastase. Incubating tracheal segments with IL-8 plus neutrophils caused GC degranulation in vitro, an effect due to activation of the neutrophils themselves (and not an effect present in the supernatant). Chemoattractant increased surface staining of elastase and the cleavage of elastase-specific fluorogenic substrate by neutrophils. Pretreatment with anti-intercellular adhesion molecule-1, anti-CD18, or anti-CD11b antibody inhibited the chemoattractant-induced GC degranulation in vitro, implicating adhesion molecules. These studies suggest that chemoattractants cause neutrophil-dependent GC degranulation involving adhesive interactions between cells, with elastase activity occurring at the cell interface, causing GC secretion. The findings, reproduced in human airways, suggest novel methods of therapeutic intervention.
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PMID:Neutrophil-dependent goblet cell degranulation: role of membrane-bound elastase and adhesion molecules. 970 90

Granulocyte colony-stimulating factor (G-CSF) has immunomodulating properties that could be beneficial for adjunctive treatment of severe infections. Cytokine release from stimulated whole blood and expression of neutrophil surface and apoptosis markers in response to G-CSF were studied in human volunteers under physiologic conditions and after ethanol pretreatment. Levels of interleukin (IL)-1 receptor antagonist and soluble tumor necrosis factor (TNF) receptor-1 were significantly increased after G-CSF, whereas TNF-alpha and IL-10 concentrations were reduced, and IL-1beta and IL-8 remained unchanged. There was a significant inhibition of neutrophil apoptosis and increased expression of complement regulatory protein CD55 without changes in CD11b, CD14, and CD59 expression. These effects were well preserved after ethanol pretreatment, which per se led to an increase in apoptosis and decreased CD55 expression. Thus, G-CSF treatment was associated with a reduction of the proinflammatory cytokine response and enhanced neutrophil survival in vivo, suggesting a therapeutic potential of G-CSF for severe infections in the nonneutropenic host.
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PMID:Inhibition of neutrophil apoptosis and modulation of the inflammatory response by granulocyte colony-stimulating factor in healthy and ethanol-treated human volunteers. 972 67

Adhesion molecules are responsible for leukocyte recruitment in injured tissues. Here, the kinetics of expression and shedding of endothelial (sE-selectin-1, sP-selectin, and sICAM-1) and neutrophil (CD11b, CD62L, and CD54) adhesion molecules was investigated by serial determinations of serum concentrations in 20 patients with elective hip arthroplasty as an exemplary condition of acute inflammation in humans. Changes were related to secretion of proinflammatory cytokines (IL-1beta, IL-6, IL-8, and TNF-alpha) as their possible inducing signals. sE-selectin-1 responded to injury with a significant increase in concentrations already after 20 min, followed by sP-selectin and sICAM-1, which increased at Hour 10 and Day 1. Expression of CD11b and CD62L acutely responded to injury (within 1 h) by a parallel increase and decrease, respectively, and normalized by Day 1. Increases in concentrations of IL-1beta and TNF-alpha preceded the increase in adhesion molecules and significantly correlated with the response of sE-selectin-1 and sICAM-1. In conclusion, the close associations between release of IL-1beta and TNF-alpha and sE-selectin and sICAM-1 shown in this kinetic study indicates a key role of these cytokines in upregulation of endothelial rather than neutrophil adhesion molecules in vivo.
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PMID:Adhesion molecules in tissue injury: kinetics of expression and shedding and association with cytokine release in humans. 975 24

Neutrophils and monocytes are the major classes of phagocytes that migrate from the blood stream and accumulate in inflamed tissues in response to various chemoattractants. Because IL-10 is a potent anti-inflammatory cytokine, we analyzed its in vitro effect on chemotaxis using an under agarose method. We found that, as compared to prednisolone, IL-10 alone was a modest inhibitor of C5a, fMLP and IL-8-induced neutrophil chemotaxis, and C5a-induced monocyte chemotaxis. However, GM-CSF pretreatment of the cells potentiated this inhibitory effect. Similarly, the IL-10 induced modulation of the beta2 integrin CD11b/CD18 adhesion molecule expression was only observed on GM-CSF-preactivated neutrophils and monocytes. Taken together, these results suggest that the migration and accumulation of phagocytes at infection sites would not be significantly affected by IL-10 given as an immunomodulatory therapy.
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PMID:Moderate inhibitory effect of interleukin-10 on human neutrophil and monocyte chemotaxis in vitro. 983 Nov 73

We investigated the mechanism or mechanisms by which rebamipide protects against the gastric mucosal inflammation associated with Helicobacter pylori. The production of interleukin (IL)-8 in association with expression of IL-8 mRNA was greatly increased in the H. pylori-infected Kato III cells in a concentration- and time-dependent manner, whereas the secretion of IL-6 and tumor necrosis factor-alpha was not detectable. The increased production of IL-8 and expression of IL-8 mRNA were significantly inhibited by rebamipide (100-1000 microM) in a concentration-dependent manner. Formyl-methionyl-leucyl-phenylalanine (1 nM), as well as conditioned medium (CM) that was produced from H. pylori-infected Kato III cells, caused an increase in surface expression of CD11b on human neutrophils and an increase in neutrophil adhesion to the human umbilical vein endothelial cells. Rebamipide also suppressed the adherence of neutrophils to endothelial cells as well as the expression of CD11b on neutrophils induced by formyl-methionyl-leucyl-phenylalanine and CM. Furthermore, CM-induced neutrophil adhesion to the endothelial cells was significantly inhibited by IL-8-neutralizing antibody, suggesting that IL-8 is implicated in the CM-induced neutrophil adhesion to the cultured human umbilical vein endothelial cells. It is concluded that rebamipide exerts its preventive effect against H. pylori-evoked gastric mucosal cell inflammation by inhibition of the neutrophil adherence to the endothelial cells as well as by suppressing the surface expression of CD11b on neutrophils and the production of proinflammatory cytokine such as IL-8 from gastric epithelial cells.
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PMID:Inhibitory effect of rebamipide on the neutrophil adherence stimulated by conditioned media from Helicobacter pylori-infected gastric epithelial cells. 986 63

The purpose of this study was to compare blood cell activation during in vitro long-term perfusion using 2 parallel in vitro extracorporeal membrane oxygenation (ECMO) systems. We compared two substantially different perfusion systems, an assistance respiratoire extra corporelle (AREC) system on one hand, containing an AREC pump, silicon tubing, and a hollow-fiber oxygenator, and a centrifugal pump system, on the other hand, containing a Biomedicus centrifugal pump, PVC tubing, and a membrane oxygenator. We measured the platelet count using an automated blood cell counter. Platelet activation was evaluated using a flow cytometric technique for the platelet membrane expression of glycoproteins and ELISA for the plasma concentration of beta-thromboglobulin (beta-TG), a platelet specific protein released into the blood upon platelet activation. The neutrophil count was assayed using an automated blood cell counter and the plasma concentration of cytokines using an ELISA kit. A significant difference between the two systems was observed in terms of the platelet membrane expression of glycoprotein (GP)Ib (p=0.0001) and GPIIb/IIIa (p=0.0037), indicating a lower degree of platelet activation in the AREC system. The concentration of neutrophils was significantly lower in the centrifugal system (p=0.002) compared to the AREC system. The neutrophil membrane expression of CD11b was significantly lower (p=0.0067) in the AREC system, indicating a lower degree of neutrophil activation compared to the centrifugal pump system. A significantly lower degree of hemolysis, as expressed by plasma hemoglobin, was observed in the AREC pump system (p=0.0491). In conclusion, lower degrees of the platelet membrane expression of GPIb and GPIIb/IIIa and of the neutrophil membrane expression of CD11b were observed in the AREC system, indicating a lower degree of platelet and neutrophil activation in this system. No significant difference between the two systems as to the plasma concentration of interleukin (IL)-1beta, IL-6, or IL-8 could be recorded. Further studies are warranted to specify the role of each individual component of the two systems.
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PMID:Induced cell trauma during in vitro perfusion: a comparison between two different perfusion systems. 987 97

Crohn's disease (CD) lesions are characterized by a marked neutrophilic infiltrate associated with enhanced mucosal IL-8, contrasting with low serum IL-8 levels. The aim of this study was to investigate the effects of circulating GROalpha and IL-8 on neutrophil priming and migration. The expression of surface molecules involved in rolling (CD62L, CD15) and firm adhesion (Mac-1 and LFA-1) to endothelial cells was assessed by flow cytometry, while the chemotactic response of PMN to IL-8 and to fMLP was investigated in a Boyden chamber assay. In addition, IL-8 and GROalpha levels were determined by ELISA in plasma samples and in culture supernatants of purified polymorphonuclear neutrophils (PMN) and peripheral blood mononuclear cells (PBMC) from patients with CD and healthy blood donors. This study revealed an upregulation of CD11b (Mac-1) membrane expression on circulating PMN from patients with CD, as assessed by the mean fluorescence intensity which reflects antigen density. Furthermore, an enhanced chemotactic response towards both fMLP and IL-8 of PMN from CD patients was observed. Despite often undetectable levels of circulating IL-8, all plasma samples were positive for GROalpha, with a significant increase in CD patients when compared to donors. In vitro, equivalent concentrations of GROalpha were able to increase the IL-8 driven chemotaxis of PMN. In conclusion, blood PMN from patients with CD showed an enhanced capacity to be recruited into inflammed intestinal mucosa, which could be due to an increased expression of CD11b (Mac-1) as well as an increased chemotactic response toward fMLP or IL-8. This priming effect of PMN in CD may partly occur through elevated circulating GROalpha levels.
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PMID:Circulating growth-regulator oncogene alpha contributes to neutrophil priming and interleukin-8-directed mucosal recruitment into chronic lesions of patients with Crohn's disease. 988 9

Isoprostanes are metabolites of arachidonic acid found in blood under various conditions of oxidative stress. Because arachidonic acid derivatives are major mediators of inflammation, we investigated the potential inflammatory effects of iPF2alpha-III (previously 8-isoPGF2alpha) and iPE2-III (8-isoPGE2) on human polymorphonuclear granulocytes (PMN), as well as on human umbilical vein endothelial cells (HUVECs). The early activation marker CD11b on PMN and the adhesion molecules ICAM-1, E-selectin, and P-selectin on HUVECs were quantified by flow cytometry. Levels of the cytokines interleukin (IL)-6 and IL-8 were measured in the culture supernatant by enzyme-linked immunosorbent assay. Furthermore, adhesion of PMN to HUVECs was assessed. Neither isoprostane showed any direct stimulatory effects on PMN or HUVECs at concentrations of 0.1 or 1 microM: there was no acute elevation in expression of CD11b or P-selectin and no change of ICAM-1 or E-selectin after 4 or 24 h of incubation, respectively. The levels of interleukin IL-6 and IL-8 were also unaltered. However, PMN adhesion was significantly enhanced both after 4 and 24 h of incubation of HUVECs with iPF2alpha-III, and CD11b expression on PMN was elevated by contact of these cells with the supernatant of pre-exposed HUVECs. Neither of these actions were inhibited by an endothelin receptor antagonist (bosentan) or a combined thromboxane A2/isoprostane-receptor antagonist (SQ29548). Thus, although not having a direct pro-inflammatory potential, isoprostanes might indirectly accentuate PMN stimulation. This seems to occur via a receptor-independent mechanism, perhaps the production of an active metabolite of isoprostanes by endothelial cells.
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PMID:Indirect enhancement of neutrophil activity and adhesion to cultured human umbilical vein endothelial cells by isoprostanes (iPF2alpha-III and iPE2-III). 1048 Apr 86


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