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)

Poultry meat and eggs contaminated with Salmonella enterica serovar Enteritidis or Salmonella enterica serovar Typhimurium are common sources of acute gastroenteritis in humans. However, the exact nature of the immune mechanisms protective against Salmonella infection in chickens has not been characterized at the molecular level. In the present study, bacterial colonization, development of pathological lesions, and proinflammatory cytokine and chemokine gene expression were investigated in the liver, spleen, jejunum, ileum, and cecal tonsils in newly hatched chickens 6, 12, 24, and 48 h after oral infection with Salmonella serovar Typhimurium. Very high bacterial counts were found in the ileum and cecal contents throughout the experiment, whereas Salmonella started to appear in the liver only from 24 h postinfection. Large numbers of heterophils, equivalent to neutrophils in mammals, and inflammatory edema could be seen in the lamina propria of the intestinal villi and in the liver. Interleukin 8 (IL-8), K60 (a CXC chemokine), macrophage inflammatory protein 1 beta, and IL-1 beta levels were significantly upregulated in the intestinal tissues and in the livers of the infected birds. However, the spleens of the infected birds show little or no change in the expression levels of these cytokines and chemokines. Increased expression of the proinflammatory cytokines and chemokines (up to several hundred-fold) correlated with the presence of inflammatory signs in those tissues. This is the first description of in vivo expression of chemokines and proinflammatory cytokines in response to oral infection with Salmonella in newly hatched chickens.
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PMID:Rapid expression of chemokines and proinflammatory cytokines in newly hatched chickens infected with Salmonella enterica serovar typhimurium. 1503 38

Interleukin-8 (IL-8), a member of CXC chemokine family, has been found to play an important role in the pathogenesis of atherosclerosis. Tumor necrosis factor-alpha (TNF-alpha) is involved in the development and progression of atherosclerosis as well. In this study, we investigated whether and how azelnidipine, a newly developed long-acting calcium antagonist, could inhibit TNF-alpha-induced IL-8 expression in human umbilical vein endothelial cells (HUVEC). TNF-alpha significantly increased intracellular reactive oxygen species (ROS) generation in HUVEC, which was completely blocked by azelnidipine or apocynin, an inhibitor of NADPH oxidase. Azelnidipine also completely prevented TNF-alpha-induced increase in NADPH oxidase activity in HUVEC. Further, azelnidipine was found to significantly inhibit activator protein-1 (AP-1) promoter activity and IL-8 expression in TNF-alpha-exposed HUVEC. An inhibitor of AP-1, curcumin, or an anti-oxidant, N-acetylcysteine, also inhibited the TNF-alpha-induced IL-8 expression in HUVEC. These results demonstrated that azelnidipine inhibited TNF-alpha-induced IL-8 expression in HUVEC by blocking NADPH oxidase-mediated ROS generation and subsequent AP-1 activation. Our present study suggests that azelnidipine may play a protective role in the development and progression of atherosclerosis through its anti-oxidative properties.
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PMID:Azelnidipine, a newly developed long-acting calcium antagonist, inhibits tumor necrosis factor-alpha-induced interleukin-8 expression in endothelial cells through its anti-oxidative properties. 1507 61

The identification of chemokines has profoundly changed the way we interpret the immune response, elucidating the mechanism by which inflammatory cells are recruited to the site of infection by local secretion of chemoattractants such as CXC chemokine ligand 8 (CXCL8)/interleukin-8, chemokine ligand 2 (CCL2)/monocyte chemoattractant protein 1. This novel view of the immune response has been remodeled further following observations that lymphoid tissue development derives from the coordinated secretion of homeostatic chemokines such as CCL19, CCL21, and CXCL13, which mediate recruitment and clustering of the cells involved in lymphoid organogenesis. The study of primary immunodeficiencies has demonstrated that the number of circulating leukocytes is dependent on migration amongst bone marrow, blood circulation, and inflamed tissues. Defects of leukocyte adhesion and chemotaxis as a result of mutations of beta2-integrins lead to abnormal leukocytosis and susceptibility to skin infections, as observed in leukocyte adhesion deficiency. Conversely, neutropenia in children with myelokathexis is a result of leukocyte retention in the bone marrow because of the mutations of CXC chemokine receptor 4, which affect the capacity of cells to recirculate between blood and bone marrow. Moreover, the identification of the genetic basis of primary immunodeficiencies has shown that many primary immunodeficiencies such as Wiskott-Aldrich syndrome and common variable immunodeficiencies are characterized by altered migration of leukocytes and/or disregulation of cellular response to chemokines. This paper will be focused on the interpretation of primary immunodeficiencies as defects in leukocyte circulation between blood and primary and secondary organs.
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PMID:Leukocyte circulation: one-way or round-trip? Lessons from primary immunodeficiency patients. 1507 52

The chemokine dose and the time period during which the chemotactic gradient is established determine the number of leukocytes that infiltrate inflamed tissues. At suboptimal chemokine concentrations, neutrophils may require a priming agent or a second stimulus for full activation. An interesting mode of cooperative action to reach maximal migration is synergy between chemokines. This was first observed between the plasma CC chemokine regakine-1 and the tissue CXC chemokine ligand interleukin-8 (IL-8/CXCL8) in neutrophil chemotaxis. Addition of antibodies against IL-8 or regakine-1 in the Boyden microchamber assay abrogated this synergy. Other CC chemokines, such as CC chemokine ligand-2 monocyte chemotactic protein-1 (MCP-1/CCL2), MCP-2 (CCL8), and MCP-3 (CCL7) as well as the CXC chemokine receptor-4 (CXCR4) agonist stromal cell-derived factor-1alpha (SDF-1alpha/CXCL12), also dose-dependently enhanced neutrophil chemotaxis toward a suboptimal concentration of IL-8. These chemokines synergized equally well with the anaphylatoxin C5a in neutrophil chemotaxis. Alternatively, IL-8 and C5a did not synergize with an inactive precursor form of CXCL7, connective tissue-activating peptide-III/CXCL7, or the chemoattractant neutrophil-activating peptide-2/CXCL7. In the chemotaxis assay under agarose, MCP-3 dose-dependently increased the migration distance of neutrophils toward IL-8. In addition, the combination of IL-8 and MCP-3 resulted in enhanced neutrophil shape change. AMD3100, a specific CXCR4 inhibitor, reduced the synergistic effect between SDF-1alpha and IL-8 significantly. SDF-1alpha, but not MCP-1, synergized with IL-8 in chemotaxis with CXCR1-transfected, CXCR4-positive Jurkat cells. Thus, proinflammatory chemokines (IL-8, MCP-1), coinduced during infection in the tissue, synergize with each other or with constitutive chemokines (regakine-1, SDF-1alpha) to enhance the inflammatory response.
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PMID:Synergy between proinflammatory ligands of G protein-coupled receptors in neutrophil activation and migration. 1507 62

The acquisition of a metastatic phenotype in breast epithelial cells is a progressive process, influenced by a large variety of cellular and soluble factors. Of these, members of the chemokine superfamily, such as CCL2, CCL5, CXCL8 and CXCL12 have been recently suggested to promote breast cancer progression. A pre-requisite for elucidation of the role of other chemokines in breast cancer progression is the characterization of chemokine and chemokine receptor expression by breast tumor cells. The present study focuses on CXCL10, a CXC chemokine that was recently suggested to have anti-malignant properties, and its corresponding receptor CXCR3. CXCR3 expression was detected in three human breast adenocarcinoma cell lines, MDA-MB-231, MCF-7 and T47D. CXCR3 expression was potently up-regulated by growing the cells under stress conditions, imposed by serum starvation. Unlike many other chemokine receptors, CXCR3 expression was not down-regulated by exposure to high concentrations (500ng/ml) of its ligand, CXCL10, but rather was promoted. CXCL10-induced up-regulation of CXCR3 expression in the three cell lines was inhibited by cycloheximide, indicating that de novo protein synthesis is required for this process. In addition to CXCR3, the secretion of CXCL10 was noted in the MDA-MB-231, MCF-7 and T47D cells. CXCL10 secretion was found to be down-regulated by IL-6, a potentially pro-malignant cytokine in breast cancer. The concomitant expression of CXCR3 and CXCL10 in breast tumor cells suggests that a CXCR3-CXCL10 axis may function in these cells, and paves the way for an in depth analysis of CXCL10-CXCR3 interactions in breast tumor cells.
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PMID:The expression of the chemokine receptor CXCR3 and its ligand, CXCL10, in human breast adenocarcinoma cell lines. 1508 42

Interleukin-6 signaling via its soluble receptor (sIL-6R) differentially regulates inflammatory chemokine expression and leukocyte apoptosis to coordinate transition from neutrophil to mononuclear cell infiltration. sIL-6R activities may, however, be influenced in vivo by the occurrence of two sIL-6R isoforms that are released as a consequence of differential mRNA splicing (DS) or proteolytic cleavage (PC) of the cognate IL-6R (termed DS- and PC-sIL-6R). Using human peritoneal mesothelial cells and a murine model of peritoneal inflammation, studies described in this work have compared the ability of both isoforms to regulate neutrophil recruitment. In this respect, DS- and PC-sIL-6R were comparable in their activities; however, these studies emphasized that IL-6 trans signaling differentially controls neutrophil-activating CXC chemokine expression. In vitro, stimulation of mesothelial cells with IL-6 in combination with either DS-sIL-6R or PC-sIL-6R showed no induction of CXC chemokine ligand (CXCL)1 (GRO alpha) and CXCL8 (IL-8), whereas both isoforms enhanced CXCL5 (ENA-78) and CXCL6 (granulocyte chemotactic protein-2) expression. Moreover, when complexed with IL-6, both isoforms specifically inhibited the IL-1 beta-induced secretion of CXCL8. These findings were paralleled in vivo, in which induction of peritoneal inflammation in IL-6-deficient (IL-6(-/-)) mice resulted in enhanced keratinocyte-derived chemokine and macrophage-inflammatory protein-2 (the murine equivalent of CXCL1 and CXCL8) levels, but reduced LPS-induced CXC chemokine (the murine equivalent of CXCL5) expression. Reconstitution of IL-6 signaling in IL-6(-/-) mice with IL-6 and its soluble receptor isoforms corrected this chemokine imbalance and suppressed overall neutrophil infiltration. These data confirm that sIL-6R-mediated signaling primarily limits neutrophil influx; however, induction of CXCL5 and CXCL6 may regulate other neutrophil responses.
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PMID:Differential regulation of neutrophil-activating chemokines by IL-6 and its soluble receptor isoforms. 1510 Mar 12

Atherosclerosis and its complications such as stroke, myocardial infraction and peripheral vascular disease, remain the major causes of morbidity and mortality in the world. Studies have showed that chemokines and adhesion molecules are involved in causing atherosclerosis by promoting directed migration of inflammatory cells. Monocyte chemoattractant protein-1 (MCP-1) is one of the key factors critical for the initiating and developing of atherosclerotic lesions. IL-8, a CXC chemokine, stimulates neutrophil chemotaxis. Aspirin is the most common drug used to prevent the complications of atherosclerosis such as stroke and coronary heart disease. In this study, we found that aspirin inhibited TNF-alpha (10 ng/ml)-induced MCP-1 and IL-8 expression at the RNA and protein levels in human umbilical vein endothelial cells (HUVECs), monocyte adhesion and transmigration, and that its inhibitory effects were not due to decreased HUVEC viability as assessed by MTT test. Aspirin at the dose as low as 10 microg/ml significantly inhibited the release of TNF-stimulated MCP-1 by 29.1% (P = 0.008) and IL-8 by 26.9% (P = 0.0146) as compared to TNF-stimulated release. Antibodies pretreatment were likely to decrease the production of MCP-1 (P < 0.0001) and IL-8 (P < 0.0001). Furthermore, aspirin (10 microg/ml) inhibited U937 cell adhesion by a 13.4% (P = 0.0119) inhibition as compared to TNF-stimulated alone. Finally, at higher concentration, aspirin also inhibited U937 migration to HUVEC by 89.1% (P = 0.0475) as compared to TNF-stimulated alone. These results in our study suggest that aspirin inhibits TNF-alpha stimulated MCP-1 and IL-8 release in HUVECs, for its additional therapeutic effects of aspirin in causing atherosclerosis.
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PMID:Aspirin inhibits monocyte chemoattractant protein-1 and interleukin-8 expression in TNF-alpha stimulated human umbilical vein endothelial cells. 1513 50

Open reading frame 74 (ORF74) of many gamma(2)-herpesviruses encodes a CXC chemokine receptor. The molecular pharmacological profile of ORF74 from herpesvirus saimiri, ECRF3, is characterized here and compared with that of the well known ORF74 from human herpesvirus 8 (HHV8). The ECRF3 receptor bound the so-called ELR (Glu-Leu-Arg) CXC chemokines (125)I-CXCL1/GRO alpha, (125)I-CXCL6/GCP-2, and (125)I-CXCL8/interleukin-8 with high affinity; but in contrast to ORF74 from HHV8, it did not bind the non-ELR CXC chemokine (125)I-CXCL10/IP10. Interestingly, the B(max) value for CXCL6/GCP-2 was 3-fold higher than the capacity for maximal binding of CXCL1/GRO alpha to ECRF3 and 85-fold higher than that of CXCL8/interleukin-8, despite similar affinities. Like ORF74 from HHV8, ECRF3 activated a broad range of pathways (G(q), G(i), and G(12/13) as well as the cAMP response element-binding protein, NF-kappa B, NFAT, and serum response element transcription factors) in a ligand-regulated manner, with CXCL6/GCP-2 being the most potent and efficacious agonist. ECRF3 signaled constitutively through G(i) and G(12/13), but surprisingly not through G(q). At the level of transcription factor activation, the serum response element was activated constitutively by ECRF3, whereas cAMP response element-binding protein, NFAT, and NF-kappa B were only ligand-regulated. The maximal signaling capacities were similar for the two receptors; however, the ligand-regulated signaling was responsible for the major part of the total ECRF3 signaling and only for a minor part of the total HHV8 ORF74 signaling. The activation pattern of ECRF3 with constitutive activation of some (but not all) of the employed pathways has not been seen before in endogenous or virus-encoded chemokine receptors. The results suggest that the unique ligand selectivity of ECRF3 among ORF74 receptors could reflect differences in the cellular tropism of the gamma(2)-herpesviruses.
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PMID:The CXC chemokine receptor encoded by herpesvirus saimiri, ECRF3, shows ligand-regulated signaling through Gi, Gq, and G12/13 proteins but constitutive signaling only through Gi and G12/13 proteins. 1515 29

IL-8 is an inflammatory CXC chemokine involved in neutrophil recruitment and activation in various inflammatory conditions. The transcriptional profile induced by IL-8 in human neutrophils was analyzed using high-density oligonucleotide arrays and compared with that of the prototypic phagocyte activator LPS. As expected, LPS induced a major effect on the cell transcriptome, upregulating 116 (0.93%) and downregulating 70 (0.56%) of the transcripts. IL-8 induced a less profound modulation of the cell transcriptome, with upregulation of 30 (0.25%) and downregulation of 6 (0.04%) of the transcripts. Although the two proinflammatory mediators induced partially overlapping transcriptional profiles (50.0% of IL-8-responsive genes were concordantly regulated by LPS), IL-8 also modulated a significant number of genes unresponsive to LPS, including soluble mediators, membrane receptors, signaling molecules, and regulators of transcription and translation. A set of IL-8-inducible genes was related to cell motility, possibly a strategy to prepare for migration into tissues. Analysis of the IL-8-responsive gene IL-1beta at the protein level revealed that transcript induction was not followed by protein production. Neutrophils stimulated with IL-8, however, showed a significant increase in IL-1beta secretion after subsequent exposure to LPS. Thus, the effect of IL-8 at the transcriptional level could provide a synergistic effect with microbial products for neutrophil activation.
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PMID:IL-8 induces a specific transcriptional profile in human neutrophils: synergism with LPS for IL-1 production. 1525 26

Chemokines critically regulate basal and inflammatory leukocyte trafficking and may play a role in angiogenesis. This review summarizes our current understanding of the regulation and potential role of the chemokines in myocardial ischemia and reperfusion. Reperfused myocardial infarction is associated with an inflammatory response leading to leukocyte recruitment, healing and scar formation. Neutrophil chemoattractants, such as the CXC chemokine CXCL8/Interleukin (IL)-8, are upregulated in the infarcted area inducing polymorphonuclear leukocyte infiltration. In addition, mononuclear cell chemoattractants, such as the CC chemokine CCL2/Monocyte Chemoattractant Protein (MCP)-1, are expressed, leading to monocyte and lymphocyte recruitment in the ischemic area. However, chemokines may have additional effects in healing infarcts beyond their leukotactic properties. We have recently described a marked transient induction of the angiostatic CXC chemokine CXCL10/Interferon-gamma inducible Protein (IP)-10 in the infarct. Upregulation of angiostatic factors, such as IP-10, in the first few hours following injury may inhibit premature angiogenesis, until the infarct is debrided and appropriate supportive matrix is formed. Suppression of IP-10 synthesis during the healing phase may allow formation of the wound neovessels, a critical process for infarct healing. Chemokine expression is also noted after a single brief ischemic insult in the absence of myocardial infarction, suggesting a potential role for a chemokine-induced inflammatory response in noninfarctive ischemic cardiomyopathy. Unlike cytokines, which have pleiotropic effects, chemokines have more specific cellular targets. Understanding of their role in myocardial infarction may allow us to design specific therapeutic strategies aiming at optimizing cardiac repair and preventing ventricular remodeling.
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PMID:The role of the chemokines in myocardial ischemia and reperfusion. 1532 May 17

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