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)

Interleukin-8 (IL-8), a C-X-C chemokine bound to endothelium proteoglycans, initiates the activation and selective recruitment of leukocytes at inflammatory foci. We demonstrate that human lactoferrin, an antimicrobial lipopolysaccharide (LPS)-binding protein, decreases both IL-8 mRNA and protein expression induced by the complex Escherichia coli 055:B5 LPS/sCD14 in human umbilical vein endothelial cells. The use of recombinant lactoferrins mutated in the LPS-binding sites indicates that this inhibitory effect is mediated by an interaction of lactoferrin with LPS and CD14s that suppresses the endotoxin biological activity. Furthermore, since dimeric IL-8 and lactoferrin are both proteoglycan-binding molecules, the competition between these proteins for heparin binding was investigated. Lactoferrin strongly inhibited the interaction of radiolabeled IL-8 to immobilized heparin, whereas a lactoferrin variant lacking the amino acid residues essential for heparin binding was not inhibitory. Moreover, this process is specific, since serum transferrin, a glycoprotein whose structure is close to that of lactoferrin, did not prevent the interaction of IL-8 with heparin. These results suggest that the anti-inflammatory properties of lactoferrin during septicemia are related, at least in part, to the regulation of IL-8 production and also to the ability of lactoferrin to compete with chemokines for their binding to proteoglycans.
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PMID:Lactoferrin inhibits the lipopolysaccharide-induced expression and proteoglycan-binding ability of interleukin-8 in human endothelial cells. 1189 48

Chemokine effects on leukocyte infiltration into the central nervous system (CNS) are key events in the inflammatory processes of neuroimmunologic and neuroinfectious diseases. Because, chemokines may play important roles in proliferation and differentiation of brain cells and in the initiation and progression of CNS inflammatory disorders, we analyzed constitutive and inflammatory-induced expression of alpha and beta chemokines in human first trimester forebrain cells. Constitutive induction of IL-8, MIP-1alpha, MIP-1beta, MCP-1 and regulated on activation, normal T-cell expressed, and secreted (Rantes) was detected in cryostat sections of embryonic forebrains in an age-dependent manner. Dissociated cell cultures were studied for spontaneous chemokine induction and after stimulation with the trypanosome lymphocyte triggering factor (TLTF), a novel trypanokine secreted by African trypanosomes that triggers a complex of immune responses. LPS and variant surface glycoprotein (VSG) were used as controls. In cultures, unstimulated cells expressed minimal chemokine levels except for Rantes. In response to TLTF and LPS, but not VSG, all chemokines were highly induced at the mRNA and protein levels in a dose- and age-dependent manner. Combined assays (in situ hybridization and immunohistochemistry) revealed that astrocytes and neurons are major sources for chemokines. These results illustrate the ability of resident brain cells to constitutively express chemokine genes, which may suggest an important role for chemokines during brain development. Furthermore, TLTF-induced chemokine expression in astrocytes and neurons indicate the capacity of TLTF to provoke neuroinflammation in the brain, which may have important therapeutic implications for the neurological manifestations of African trypanosomiasis.
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PMID:Constitutive and inflammatory induction of alpha and beta chemokines in human first trimester forebrain astrocytes and neurons. 1200 70

Chemokines represent a family of potent biological mediators. Within the group of receptors mediating their effects, a promiscuous receptor has been found which is able to bind and inactivate diverse chemokines of both C-C and C-X-C families. It is co-localized with blood group antigens of the Duffy system on the same glycoprotein and expressed on red blood cells as well as post-capillary blood vessels. In the present study three aspects of Duffy pathophysiology were studied: firstly the amount of IL-8 and RANTES binding to red blood cells and its correlation to disease activity of psoriatic patients, secondly the distribution of Duffy phenotype among psoriatic patients and thirdly the expression of Duffy antigen in normal vs psoriatic skin. Red blood cells from psoriatic patients (n=50) were lysed by triton X (1%) and supernatants tested in IL-8- and RANTES sandwich-ELISA. Duffy phenotype of psoriatic patients (n=50) was assessed by typing red blood cells with specific antisera in indirect Coombs technique. For immunohistochemical detection in normal and psoriatic skin (n=10 respectively) a specific monoclonal antibody (Fy6) was used. Neither IL-8- nor RANTES-levels on red blood cells correlated to disease activity and distribution of Duffy phenotype in psoriatics was not significantly altered when compared to the normal population. Furthermore, Duffy antigen was expressed in a similar pattern in normal and psoriatic skin at all parts of vasculature, albeit much more abundantly in diseased skin. Altogether, chemokine binding to red blood cells seems of minor importance in psoriasis. However, Duffy antigen together with other binding mechanisms like proteoglycans may play a role at local level by binding locally produced chemokines. Thus biological effects of chemokines are both restricted and focussed to dermal tissue.
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PMID:The role of the Duffy antigen-related chemokine receptor in psoriasis vulgaris. 1216 May 21

Previous evidence has shown that coronary angioplasty leads to the release of inflammatory mediators. In this study, we sought to characterize the systemic inflammatory response after coronary stent implantation in patients with unstable angina by measuring different protein markers. Peripheral blood samples were taken before and 24 h, 48 h, and 7 days after successful coronary stenting in 58 patients. Several markers of acute-phase response were determined: C-reactive protein (CRP), alpha2-macroglobulin, haptoglobin, acid alpha1-glycoprotein, prealbumin and albumin. Besides, proinflammatory cytokines (tumor necrosis factor-alpha, IL-6, IL-8) and the anti-inflammatory cytokine IL-10 were also measured. We have found that coronary angioplasty with stent implantation produces a systemic inflammatory response with a rise in inflammation markers concentration. CRP plasma levels declined 1 week after the intervention, but the other marker levels were even higher after 7 days. IL-6 was the only cytokine whose plasma levels significantly increased in peripheral blood after stenting, with a rise after 24 h, maintained after 48 h, and decreased to near-basal levels after 1 week. There was a good correlation between CRP and IL-6 plasma levels (r=0.5, p<0.001). IL-10 levels were slightly decreased after 24 h. Although no significant differences in the means at different time points were found, there was a decrease in IL-10 in most patients 24 h after the intervention. These results indicate that coronary stent implantation induces a systemic inflammatory reaction, with a temporal increase in the concentration of the inflammation markers, especially CRP and IL-6. Since these markers had been previously used as prognostic markers, this needs to be taken into account in patients undergoing stent implantation.
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PMID:Inflammatory response to coronary stent implantation in patients with unstable angina. 1239 2

To investigate immune-endocrine interactions between the embryo and the mother early in pregnancy, we examined the effects of human chorionic gonadotropin (HCG) on IL-8 production by peripheral blood mononuclear cells (PBMC). Recombinant HCG promoted IL-8 secretion by PBMC derived from nonpregnant women. The induction of IL-8 mRNA expression was observed after 30 min of HCG stimulation. Adsorption of the HCG with anti-HCG antibodies confirmed the specificity of this effect. The translocation of nuclear factor kappaB into the nucleus and subsequent IL-8 production were observed mainly in monocytes, and IL-8 production was reduced when a proteasome inhibitor was added to inactivate nuclear factor kappaB. Although fluorescein isothiocyanate-labeled HCG was bound to the majority of monocytes, cell surface expression of HCG receptor was hardly detected. IL-8 production by HCG was not affected by inhibitors of protein kinases A and C. In contrast, this stimulation was attenuated by D-mannose, which inhibits binding to C-type lectins. The basal IL-8 production by PBMC from women early in pregnancy was significantly elevated, compared with that from nonpregnant women. This study showed that human monocytes respond to HCG and secrete IL-8 through a pathway different from the HCG receptor system, suggesting that this glycoprotein hormone can react with not only endocrine cells but also immune cells early in pregnancy, probably via primitive systems such as C-type lectins.
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PMID:Human chorionic gonadotropin (HCG) activates monocytes to produce interleukin-8 via a different pathway from luteinizing hormone/HCG receptor system. 1241 93

Gp-340 is a glycoprotein belonging to the scavenger receptor cysteine rich (SRCR) group B family. It binds to host immune components such as lung surfactant protein D (SP-D). Recent studies found that gp-340 interacts directly with pathogenic microorganisms and induces their aggregation, suggesting its involvement in innate immunity. In order to investigate further its potential immune functions in the appropriate cell lines, the expression of gp-340 in four conventional immune cell lines (U937, HL60, Jurkat, Raji), and two innate immune-related epithelial cell lines (A549 derived from lung and AGS from stomach), was examined by RT-PCR and immunohistochemistry. The resting immune cell lines showed weak or no gp-340 mRNA expression; while the two epithelial cell lines expressed gp-340 at much higher level, which was differentially regulated by phorbol myristate acetate (PMA) treatment. In the A549 cells, gp-340 was up-regulated along with the PMA-induced proinflammatory expression of both IL-6 and IL-8. In AGS cells, PMA down-regulation of gp-340 was seen in parallel with an up-regulation of the two mature gastric epithelial specific proteins TFF1 (trefoil factor 1) and TFF2, which are implicated as markers of terminal differentiation. Analysis of the distribution of gp-340, together with the TFFs and SP-D in normal lung and gastric mucosa, supported further our in vitro data. We conclude that the differential regulation of gp-340 in the two epithelial cell lines by PMA indicates that gp-340 s involvement in mucosal defence and growth of epithelial cells may vary at different body locations and during different stages of epithelial differentiation.
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PMID:The scavenger receptor, cysteine-rich domain-containing molecule gp-340 is differentially regulated in epithelial cell lines by phorbol ester. 1245 35

Interleukin-8 (IL-8), which is a member of C-X-C chemokine subfamily, is an important activator and chemoattractant for neutrophils and has been implicated in a variety of inflammatory diseases. Numerous reports show that various cells express IL-8 mRNA and produce IL-8 protein rapidly, including monocytes, T lymphocytes, neutrophils, fibroblasts, endothelial cells and epithelial cells. The human IL-8 gene has a length of 5191 bp and contains four exons separated by three introns. It maps to human chromosome 4q12-q21. The mRNA consists of a 101 bases 5' untranslated region, an open reading frame of 297 bases, and a long 3' untranslated region of 1.2 kb. The 5' flanking region of the IL-8 gene contains potential binding sites for several nuclear factors including activated protein-1 (AP-1), activated protein-2 (AP-2), nuclear factor-gene binding (NF-kappa B), nuclear factor-interleukin-6 (NF-IL-6, also calls CAAT/enhancer-binding proteins, C/EBP), IFN regulatory factor-1 (IRF-1), hepatocyte nuclear factor-1 (HNF-1), and so on. IL-8 gene expression is regulated initially at the level of gene transcription. The rapid induction of IL-8 gene expression is likely mediated by latent transcription factors that bind the IL-8 promoter. AP-1 and NF-IL-6 physically interact with NF-kappa B, and functional cooperativity among these factors appears to be critical for optimal IL-8 promoter activity in different cell types. The IL-8 receptor (IL-8R) is a dimeric glycoprotein consisting of a 59 KDa and a 67 KDa subunit. It has been given the name CDw128. It is expressed in many different cell types including those not responding to IL-8. The receptor density is approximately 20,000/cell in neutrophils, 1,040/cell in monocytes, and 300/cell in T-lymphocytes. The IL-8R is a member of the family of G-protein-coupled receptors. There are at least two different IL-8 receptor types (CXCR1 and CXCR2). The activities of IL-8 are not species-specific. IL-8 affects the adhesion of neutrophils to the endothelium and induces the transendothelial migration of neutrophils. IL-8 also exhibits in vitro chemotactic activities against of T-lymphocytes and basophils. IL-8 gene expression can be regulated by fluid shear stress, which may play an important role in the genesis and development of both inflammation and arterosclerosis.
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PMID:[The study on the interleukin-8 (IL-8)]. 1256 82

Lactoferrin, a glycoprotein present in milk, mucosal secretions and neutrophils contributes to host defense. We have previously shown that orally given milk lactoferrin (LF) mediates anti-infectious and anti-inflammatory activities in vivo. Moreover, we have shown that LF could inhibit the LPS-induced IL-6 secretion in a human monocytic cell line, THP-1. This observation was expanded in the present study investigating the capacity of LF to inhibit cytokine mRNA expression and the involvement of nuclear transcription factor kappa B (NF-kappa B). Cells (THP-1 and Mono Mac 6 monocytic cell lines) were stimulated with Escherichia coli LPS (5-10 ng/10(6) cells) and LF was added (50-500 microg/10(6) cells) 30 min before, or after the LPS addition. By a semiquantitative RT-PCR lower levels of TNF-alpha, IL-1 beta, IL-6, and IL-8 mRNA expression were detected at the peak of the expression in THP-1 cells treated with LF. The reduction in the cytokine expression was followed by a similar reduction in the secreted cytokines as analyzed by ELISA. LF down-regulated also the IL-10 secretion (detected only in LPS-stimulated Mono Mac 6 cells). A similar level of inhibition of these cytokines was detected regardless of the time at which LF was added to the cells in relation to LPS. In addition, LF was internalized into cells and detected in the nucleoli as determined by immunostaining and immunofluorescence. Moreover, by electrophoretic mobility shift assay (EMSA) analysis LF decreased the LPS-induced binding of NF-kappa B to the TNF-alpha promoter. The results show that LF down-regulates the LPS-induced cytokine production in monocytic cells. The inhibitory mechanism is suggested to involve the interference of LF with NF-kappa B activation.
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PMID:Lactoferrin down-regulates the LPS-induced cytokine production in monocytic cells via NF-kappa B. 1265 43

The CD69 glycoprotein is an early activation antigen of T and B lymphocytes but it expression is induced in vitro on cells of most hematopoietic lineages, including neutrophils after stimulation with PMA or fMLP. In this study, we investigated whether CD69 expression on human neutrophils could be modulated by inflammatory or anti-inflammatory cytokines (IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18, G-CSF, GM-CSF, TNF-alpha, TGF-beta, IFN-alpha, IFN-gamma). Resting neutrophils from healthy subjects did not express CD69 on the cell surface; moreover, a preformed intracellular pool of CD69 was not evident in these cells. CD69 was barely detectable on these cells after overnight incubation in medium while overnight incubation with GM-CSF, IFN-gamma or IFN-alpha significantly induced CD69 expression on neutrophils with GM-CSF appearing to be the most potent inducer. This induction was dependent on a new protein synthesis as it was significantly inhibited by cycloheximide (about 50% inhibition). CD69 cross-linking on GM-CSF-primed neutrophils sinergized with LPS and increased TNF-alpha production and secretion suggesting a role for CD69-positive neutrophils in the pathogenesis and maintenance of different inflammatory diseases.
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PMID:Induction of CD69 activation molecule on human neutrophils by GM-CSF, IFN-gamma, and IFN-alpha. 1271 36

Proinflammatory cytokines released from monocytes/macrophages, in particular tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6, and IL-8 seem to play an important role in Inflammatory Bowel Disease (ulcerative colitis and Crohn's disease). Endotoxins or lipopolysaccharides, derived from the outer membrane of Gram-negative bacteria interact with CD14 on surface membrane of macrophages, thus triggering a signal cascade, which leads to the production and release of proinflammatory cytokines, particularly TNF-alpha. Therefore, in IBD, lipopolysaccharides could play a pathogenic role. In this respect, plasma endotoxins have been demonstrated in a not negligible percentage of patients with ulcerative colitis and in their unaffected relatives. The presence of circulating endotoxins could be due, at least in part, to the impaired natural immunity in either patients with ulcerative colitis or in their first degree unaffected relatives. Lactoferrin is an iron-binding glycoprotein, which binds to the lipid A region of lipopolysaccharide with a high affinity and this interaction prevents the binding of lipopolysaccharide to CD14, thus inhibiting the release of proinflammatory cytokines. Therefore, based on the possible pathogenic role exerted by endotoxins in ulcerative colitis, lactoferrin may deserve attention as a possible therapeutical agent in experimental models of Inflammatory Bowel Disease.
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PMID:Immune abnormalities and endotoxemia in patients with ulcerative colitis and in their first degree relatives: attempts at neutralizing endotoxin-mediated effects. 1287 Nov 78


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