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)

Because of the association of burn injury with subsequent bacterial infection, numerous studies have been performed characterizing neutrophil function in burn injury. These studies provide a picture of intravascular complement activation, neutrophil-C5a interactions, and consequent disordered cellular function. Neutrophil dysfunction includes suppressed random and C5a-directed migration and hyperresponsiveness to oxidative stimuli. These observations do not explain the histologic and functional involvement of neutrophils in ARDS and perhaps other organ failure states. Circumstantial and extrapolated information suggests that macrophage-lineage cells function as regulators of neutrophil function within matrix environments in burn injury. Elevated endotoxin levels have been found in burned patients, which would support the notion of endotoxin-stimulated monocytes/macrophages as inducing neutrophil migration into connective tissue matrices (LTB4 and IL-8), inducing prolonged oxidant production (TNF-alpha, GM-CSF), and inducing neutrophil release of regulatory substances from neutrophils (G-CSF). This information suggests a variety of experimental approaches to testing this hypothesis.
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PMID:Neutrophil disorders in burn injury: complement, cytokines, and organ injury. 225 97

Interleukin (IL)-10 is a potent immunosuppressant of monocyte/macrophage function and may help control the inflammatory response induced by bacterial infection. To analyze whether IL-10 is detectable in plasma of patients with septic shock and to evaluate its relationship with endotoxin (lipopolysaccharide [LPS])-induced and monocyte/macrophage-induced inflammatory response, plasma IL-10, tumor necrosis factor (TNF)-alpha, IL-1 beta, IL-6, IL-8, LPS, and neopterin were studied in 24 patients with septic shock and in 12 critically ill patients. Eighty-three percent of patients with septic shock and 25% of critically ill patients had detectable levels of IL-10 (P < .001). There was a significant correlation between plasma IL-10, neopterin (r = .72), TNF-alpha (r = .76), IL-6 (r = .68), and IL-8 (r = .61) levels in patients with septic shock. Monocyte/macrophage activation leads to massive secretion of IL-10, which, however, seems to be unable to control the increased production of proinflammatory mediators during septic shock.
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PMID:Interleukin-10 and the monocyte/macrophage-induced inflammatory response in septic shock. 756 Dec 9

Human Gingival Fibroblasts (HGF) may have an important role in the orchestration of immuno-participant cells infiltrating the gingiva in response to continuously recurring bacterial infection. To examine the cytokine network regulating HGF-derived interleukin (IL)-8, a potent neutrophil chemotactic cytokine, we analyzed the effects of inflammatory cytokines alone and in combination on IL-8 production by HGF. IL-1 beta, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), IL-6, and IL-8 were used as stimulants. HGF secreted IL-8 in a dose-dependent manner after stimulation with either IL-1 beta or TNF-alpha, but not with IFN-gamma or IL-6. Furthermore, IL-8 itself did not affect IL-8 mRNA accumulation in HGF in an autocrine manner. The combination of IL-1 beta and TNF-alpha synergistically enhanced the secretion of IL-8, whereas IFN-gamma suppressed IL-8 secretion by IL-1 beta- or TNF-alpha-stimulated HGF. These effects were also observed at each level of IL-8 mRNA expression in HGF. IL-8 secretion by cytokine-stimulated HGF was not influenced by the inhibition of PGE2 synthesis with indomethacin, indicating that endogenous PGE2 was not involved in IL-8 production by HGF. These results indicate that IL-8 production by HGF is synergistically stimulated by specific cytokines, IL-1 beta and TNF-alpha, and suggest that these stimulatory effects are down-regulated by IFN-gamma at the transcriptional level through PGE2-independent pathways. Thus, neutrophil-mediated processes in periodontal disease may be regulated in part by HGF in the cytokine network of immuno-participant cells.
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PMID:Cytokine-dependent synergistic regulation of interleukin-8 production from human gingival fibroblasts. 785 22

Interleukin (IL)-8 is a macrophage-derived neutrophil chemotactic factor that plays an important role in the recruitment of neutrophils to inflammatory loci. Hence, expression of IL-8 by alveolar macrophages may be a significant factor in host defense in the lung and in the pathogenesis of pneumonia in swine. To initiate molecular studies of IL-8 regulation in pigs, we cloned IL-8 cDNA and examined the regulation of its mRNA in alveolar macrophages. The porcine IL-8 cDNA consists of 1491 base pairs including a coding region of 309 base pairs. The deduced amino acid sequence was 75 and 81% similar to human and rabbit IL-8, respectively. Resting macrophages contained low levels of IL-8 mRNA, which increased markedly after exposure to bacterial lipopolysaccharide (LPS). LPS induction of IL-8 was direct, not mediated through elevation of tumor necrosis factor or interleukin-1. The effect of LPS on IL-8 expression was dose dependent, and induction was observed at a concentration of 10 pg/ml. IL-8 mRNA expression was detectable within 0.5 h after stimulation with LPS, peaked at 3-6 h at about 30-fold higher levels than in resting cells, and was maintained for 24 h. Secreted IL-8, measured by neutrophil chemotaxis, was induced within 4 h by LPS, and accumulated in the media throughout the 24-h period. The mechanism of induction of IL-8 mRNA appeared to involve transcription and RNA processing. Nuclear run-on analysis showed that the IL-8 gene was actively transcribed in noninduced cells; upon stimulation with LPS, the rate of IL-8 transcription was increased about 4-fold. A single mature mRNA species was detected by primer extension analysis. The half-life of IL-8 mRNA transcripts in aveolar macrophages was approximately 2 h and did not change after LPS stimulation. The ability of LPS to induce IL-8 expression was suppressed by recombinant human IL-4 and dexamethasone in a concentration-dependent manner. These observations indicate that the expression of IL-8 is an early event in the sequelae to bacterial infection in the lung.
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PMID:Regulation of interleukin-8 expression in porcine alveolar macrophages by bacterial lipopolysaccharide. 827 81

Cytokines presently known to be involved in systemic bacterial infection are tumour-necrosis factor (TNF), interleukin (IL)-1, IL-6, IL-8 and interferon-gamma (IFN-gamma) and the counterregulatory molecules soluble TNF receptor (sTNFR) and IL-1 receptor antagonist (IL-1 Ra). In animal models TNF, IL-1 and IFN-gamma mediate organ damage, low blood pressure and fatality, whereas IL-6 is involved in infection-related manifestations, like the production of acute-phase protein and fever, and IL-8 is chemotactic to granulocytes. TNF and IL-1 increase expression of adhesion molecules on endothelial cells and influence a number of components of the haemostatic system in favour of coagulation. The presence of cytokines in the circulation is characterized by sequential releases of TNF, IL-1 and IL-6/IL-8; however, many variations of this pattern exist during human infection. In experiments as well as in human infection TNF, IL-1, IL-6, IL-8 and IFN-gamma have been detected, and levels of TNF, IL-6 and IL-8 have been found to be associated with the severity of the disease. Collectively, TNF, IL-1 and IFN-gamma emerge as mediators of systemic infection and septic shock whereas IL-6 and IL-8 are related to other manifestations of infection. Counteracting molecules like sTNFR are released after somewhat of a delay following TNF and IL-1Ra is released concomitantly with IL-1. Probably these factors modulate the cytokine effect although their true potency in natural infection has yet to be clarified. In granulocytopenic infections TNF, IL-1, IL-6 and IL-8 can be detected in serum, and levels of TNF and IL-6 are even higher than in the normal situation in experimental animals. Antibodies to TNF inhibit bacteria-induced fatality in granulocytopenic mice. Altogether, few data related to the granulocytopenic situation are available. However, it is reasonable to believe that the altered development of granulocytopenic infections is due to changes in the cellular constitution and not to changes in cytokine production.
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PMID:Cytokine mediators of septic infections in the normal and granulocytopenic host. 831 84

Gastric infection with Helicobacter pylori is frequently characterized by neutrophil infiltration. The production of the neutrophil-activating peptide (NAP-1/IL-8) and mucosal IgA autoantibodies to IL-8 by human antral biopsies have been examined during short-term in vitro culture. Detectable IL-8 was secreted by 84% of H. pylori-negative patients with normal antral mucosa (range < 0.07-61.5 ng/mg biopsy protein, n = 19). Concentrations in 4 patients with reactive gastritis and 10 with inactive gastritis were not significantly different from subjects with normal mucosa. In H. pylori-positive patients with active gastritis and neutrophil infiltration into the epithelium (n = 17) IL-8 secretion was significantly increased relative to subjects with normal mucosa (P < 0.0001), inactive gastritis (P < 0.001) and reactive gastritis (P < 0.01). IL-8 concentrations in active gastritis were significantly correlated with the extent of epithelial surface degeneration (r = 0.64). IgA autoantibodies were present in 19 patients (13 active, 4 inactive gastritis) and concentrations were significantly correlated with IL-8 production (P < 0.001). Gastric synthesis of IL-8 is likely to be an important factor in regulating mucosal neutrophil infiltration and activation in patients with H. pylori infection. The local production of IgA antibodies to IL-8 may represent a down-regulatory response of the host to limit mucosal damage associated with a chronic bacterial infection.
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PMID:Gastric interleukin-8 and IgA IL-8 autoantibodies in Helicobacter pylori infection. 841 74

Sickle-cell adherence to endothelium has been hypothesized to initiate or contribute to microvascular occlusion and pain episodes. Adherence involves plasma proteins, endothelial-cell adhesion molecules, and receptors on sickle erythrocytes. It has previously been reported that sickle reticulocytes express the alpha 4 beta 1 integrin receptor and bind to cytokine-activated endothelium via an alpha 4 beta 1/vascular-cell adhesion molecule-1 (VCAM-1) interaction. To elucidate other roles for alpha 4 beta 1 in sickle-cell adherence, the ability of activated alpha 4 beta 1 to promote adhesion to endothelium via a ligand different than VCAM-1 was explored. Adherence assays were performed under dynamic conditions at a shear stress of 1 dyne/cm2. Preincubation of sickle erythrocytes with phorbol 12,13-dibutyrate (PDBu) increased adherence of sickle cells eightfold as compared with untreated sickle cells. Normal erythrocytes, whether treated with PDBu or not, did not adhere to the endothelium. Activating anti-beta 1 antibodies 4B4 and 8A2 also increased the adhesion of sickle, but not normal, red blood cell (RBC) adhesion to endothelium. Anti-alpha 4 antibodies HP1/2 and HP2/1, inhibitory antibody 4B5, or an RGD peptide inhibited sickle-cell adherence induced by PDBu. Additional studies were undertaken to examine if fibronectin, a ligand for activated alpha 4 beta 1, was involved in PDBu-induced sickle erythrocyte adherence. Adherence of PDBu-treated sickle cells was completely inhibited by the CS-1 peptide of fibronectin. Fibronectin was detected on the surface of washed endothelium using an antifibronectin antibody in enzyme-linked immunosorbent assays. Antifibronectin antibody pretreatment of endothelial cells inhibited PDBu-induced adherence by 79% +/- 17%. Incubation of sickle RBCs with exogenous fibronectin after PDBu treatment inhibited adherence 86% +/- 8%. Taken together, these data suggest that endothelial-bound fibronectin mediates adherence of PDBu-treated sickle cells. Interleukin-8 (IL-8), a chemokine released in response to bacterial infection, viral infection, or other injurious agents, and known to activate integrins, also increased adherence of sickle erythrocytes to endothelial cells via fibronectin. This novel adherence pathway involving sickle-cell alpha 4 beta 1 activated by PDBu or IL-8 may therefore be relevant in vivo at vascular sites that produce IL-8 or similar agonists in response to vascular injury or immune activation. These observations describe ways in which inflammation and immune responses cause vasoocclusive complications in sickle-cell disease.
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PMID:Phorbol ester stimulation increases sickle erythrocyte adherence to endothelium: a novel pathway involving alpha 4 beta 1 integrin receptors on sickle reticulocytes and fibronectin. 894 72

IL-8, a potent neutrophil chemotactic agent, is known to be a key mediator in several inflammatory diseases. We found that 10 ng/ml of serum-activated LPS (Escherichia coli) efficiently up-regulated IL-8R on the surface of neutrophils within 30 min of LPS stimulation by 115 to 120% through de novo protein synthesis. After 30 min of LPS stimulation, reduction of IL-8R level was initiated and the normal level was restored within 2 h of LPS interaction. EDTA or EGTA and bestatin separately inhibited the receptor down-regulation by 98%, indicating the involvement of metalloprotease(s), more specifically an aminopeptidase in the process. Induction and subsequent reduction of IL-8 binding in serum-activated LPS-stimulated cells have been demonstrated in autoradiography. Intracellular Ca2+ level in these stimulated neutrophils was increased and decreased with alteration of IL-8R level. Although IL-8 binding was drastically reduced, the total IL-8R level, as detected by anti-IL-8R Ab measured by 125I-labeled anti-rabbit IgG, remained almost unaltered, indicating that minimal proteolysis occurred in IL-8R. Anti-IL-8R Ab and IL-8 itself could prevent this down-regulation significantly, suggesting that the susceptible epitope(s) might be in the IL-8 binding domain of the receptor. Under Ca2+-depleted conditions, the proteolysis was inhibited, which was accelerated upon addition of 1 mM of CaCl2. The study demonstrates that LPS-induced up-regulation of IL-8R leads to amplified IL-8-mediated biologic responses of neutrophils that are restored to normal level by activation of a Ca2+-dependent aminopeptidase. This may be useful for understanding the regulation of LPS-mediated inflammatory responses of neutrophils during bacterial infection.
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PMID:A Ca2+-dependent autoregulation of lipopolysaccharide-induced IL-8 receptor expression in human polymorphonuclear neutrophils. 901 72

Cytokine levels in nasal and lower airways in young cystic fibrosis (CF) patients were compared with those in controls. Nasal (NLF) and bronchoalveolar (BALF) lavage fluids were obtained from children with or without CF who were undergoing bronchoscopy for clinical indications. In NLF, neither inflammatory cells nor cytokine concentrations differed between patients and controls. However, interleukin (IL)-8 levels in infected BALF from children with CF were markedly elevated compared with levels in infected and uninfected controls, even after standardization of IL-8 concentrations to bacterial counts. BALF IL-6 was modestly elevated in infected CF patients compared with uninfected but not infected controls; IL-10 did not differ among the groups. NLF and BALF IL-8 levels were not significantly correlated. Excessive airway inflammation in early CF thus appears to be confined to the lower respiratory tract, and IL-8 levels are markedly increased in children with CF compared with control children with a bacterial infection of the lower airways.
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PMID:Nasal and bronchoalveolar lavage fluid cytokines in early cystic fibrosis. 904 36

Interfering with the endotoxin-mediated cytokine cascade is thought to be a promising approach to prevent septic complications in gram-negative infections. The synthetic lipid A analog SDZ MRL 953 has been shown to be protective against endotoxic shock and bacterial infection in preclinical in vivo models. As part of a trial of unspecific immunostimulation in cancer patients, we conducted a double-blind, randomized, vehicle-controlled phase I trial of SDZ MRL 953 to investigate, first, its biologic effects and safety of administration in humans and, second, its influence on reactions to a subsequent challenge of endotoxin (Salmonella abortus equi). Twenty patients were treated intravenously with escalating doses of SDZ MRL 953 or vehicle control, followed by an intravenous application of endotoxin (2 ng/kg of body weight [BW]). Administration of SDZ MRL 953 was safe and well-tolerated. SDZ MRL 953 itself increased granulocyte counts and serum levels of granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6), but not of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), IL-1beta, and IL-8. Compared with vehicle control, pretreatment with SDZ MRL 953 markedly reduced the release of TNF-alpha, IL-1beta, IL-8, IL-6, and G-CSF, but augmented the increase in granulocyte counts to endotoxin. Induction of tolerance to the endotoxin-mediated cascade of proinflammatory cytokines by pretreatment with SDZ MRL 953 in patients at risk may help to prevent complications of gram-negative sepsis.
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PMID:Downregulation of the proinflammatory cytokine response to endotoxin by pretreatment with the nontoxic lipid A analog SDZ MRL 953 in cancer patients. 926 88

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