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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The small inducible gene (SIG) family encodes related proteins that are involved in the overlapping processes of coagulation, inflammation, immune response, and wound repair. This family contains two branches, termed CXC and CC, which are distinguished by whether or not the first two of four conserved cysteine residues are separated by an additional amino acid residue. All of the CXC SIGs map to chromosome 4, including those encoding beta-thromboglobulin (beta TG) and platelet factor 4 (PF4), both of which are expressed by megakaryocytes in a tissue-specific fashion. Both of these latter two genes have been previously reported to be duplicated, there being a PF4 and a PF4alt gene, and a beta TG1 and beta TG2 gene. We now show by pulse-field gel electrophoresis (PFGE) that the beta TG genes are closely linked to the PF4 genes and to other previously mapped CXC SIGs, namely IL8 (encoding interleukin-8), GRO1 (encoding a cytokine also called melanoma growth-stimulatory activity), and two related genes GRO2 and GRO3, on a single 700-kb Sfil fragment localized to chromosome bands 4q12-q13. The only CXC SIG not linked to this cluster is that encoding gamma-interferon-induced 10-Kd protein (INP10), which has been previously localized to 4q21. Analysis of lambda genomic clones demonstrate that the beta TG1 and PF4 genes are separated by less than 7 kb, and the beta TG2 and PF4alt genes by approximately 5 kb. Within each beta TG/PF4 duplication, the beta TG-like gene is upstream of its linked PF4-like gene. Thus, the beta TG/PF4 genes appear to form a close-linked complex expressed in a megakaryocyte-specific fashion. Further genomic studies may provide additional insights into the regulation of the tissue-specific expression of the beta TG/PF4 gene complex, while further analysis of the linked CXC SIG cytokine family may provide further understanding of their evolutionary history.
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PMID:Genes for beta-thromboglobulin and platelet factor 4 are closely linked and form part of a cluster of related genes on chromosome 4. 131 86

Alveolar macrophages (AM) mediate lung inflammation by producing lipid and peptide molecules that attract neutrophils (PMN) to the lung. Recently we described two porcine proteins called alveolar macrophage-derived chemotactic factors, AMCF-I and -II, that are potent, efficacious, and specific PMN chemoattractants both in vitro and in vivo. We report here the cloning of the full-length cDNAs which code for each protein. Porcine AM were stimulated for 4 h in vitro with Escherichia coli endotoxin (LPS), and a cDNA library was created from poly(A)(+)-selected mRNA. Specific oligonucleotide probes for AMCF-I and AMCF-II were amplified from the porcine AM cDNA library by the polymerase chain reaction using degenerate oligonucleotide primer pairs derived from the N-terminal amino acid sequences of the proteins. These probes were used to isolate 2 full-length cDNAs of 1466 (AMCF-I) and 1515 (AMCF-II) base pairs. Both cDNAs code for proteins with four cysteine residues containing the C-X-C sequence characteristic of the intercrine-alpha family of neutrophil chemoattractants. AMCF-I shares 74% identity with human IL-8 and 84% identity with rabbit IL-8, and likely represents the porcine homologue of IL-8. By contrast, AMCF-II has no obvious human homologue. AMCF-II shares 53% identity with human neutrophil activating peptide 2. Its shared identity with the GRO-related proteins is as high as 61% (rat CINC/GRO), and its shared identity with the 78 amino acid epithelial cell-derived neutrophil activator (ENA-78) is 67%. AMCF-II may represent a new member of the intercrine-alpha family of neutrophil chemoattractants.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular cloning of porcine alveolar macrophage-derived neutrophil chemotactic factors I and II; identification of porcine IL-8 and another intercrine-alpha protein. 142 Jan 65

Neutrophil elicitation into tissue is an essential element of the host defense in response to various stimuli, including, tissue injury, infection, or cancer. This event has gained renewed interest with the discovery of a family of small polypeptides (less than 10 kD). The salient features of these cytokines are the presence of four cysteine amino acids (first two separated by one amino acid; C-X-C) and their ability to induce neutrophil chemotaxis and activation. Recently, our laboratories have discovered a new member of this C-X-C chemotactic cytokine supergene family, neutrophil-activating peptide, ENA-78. ENA-78 shares significant amino acid sequence homology with neutrophil activating peptide-2 (NAP-2; 53%), growth regulated oncogene/melanoma growth stimulatory activity (GRO alpha; 52%), and IL-8 (22%). In addition, ENA-78 appears to activate neutrophils through the IL-8 receptor. Since both in vitro and in vivo biological fluids may contain an array of chemotactic cytokines that may be relevant to the activation and chemotaxis of neutrophils, we have developed a highly specific and sensitive sandwich ELISA for the detection of ENA-78.
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PMID:The detection of a novel neutrophil-activating peptide (ENA-78) using a sensitive ELISA. 142 26

Cytokine-stimulated human osteosarcoma cells (MG-63) secrete several related chemotactic factors, including the neutrophil-activating protein interleukin 8 (IL-8) and the monocyte chemotactic protein (MCP)-1. We describe the isolation and characterization of two novel monocyte chemotactic factors from this tumor cell line. Although these proteins copurified with MCP-1 and IL-8 on heparin-Sepharose, they could be separated by cation-exchange fast protein liquid chromatography and reverse-phase high-performance liquid chromatography. The corresponding 7.5- and 11-kD proteins were NH2-terminally blocked but were identified by sequencing peptide fragments. They showed a primary structure mostly related to that of MCP-1 and were therefore designated MCP-2 and MCP-3, respectively. These molecules can be classified in a subfamily of proinflammatory proteins characterized by the conservation of cysteine residues. MCP-2 and MCP-3 are also functionally related to MCP-1 because they specifically attract monocytes, but not neutrophils, in vitro. The chemotactic potency (specific activity) was comparable for all three MCPs. Intradermal injection of these proteins in rabbits resulted in selective monocyte recruitment in vivo. Since tumor cells are good producers of leukocyte chemotactic factors, it could be questioned whether these molecules can indirectly control tumor growth by attracting leukocytes or whether they rather promote invasion by the secretion of proteases from the attracted cells.
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PMID:Structural and functional identification of two human, tumor-derived monocyte chemotactic proteins (MCP-2 and MCP-3) belonging to the chemokine family. 161 66

An important process in the immune response is the migration of different populations of lymphocytes at the proper time to sites of antigenic challenge. Although several chemoattractants are known for broad classes of lymphocytes, such as T and B cells, the process by which lymphocytes of specific subsets, such as helper, cytotoxic or memory T cells, migrate to the appropriate sites remains obscure. Interleukin-8 is a chemoattractant for T cells and neutrophils and is a member of a superfamily of soluble molecules related by a conserved motif containing four cysteine residues. IL-8 and related molecules, including platelet factor 4, constitute the C-X-C class of the superfamily and a group of cytokines produced by haematopoietic cells constitute the RANTES/sis or C-C class. The roles of most of these molecules are not well known, although murine MIP-1 alpha of the C-C branch is a specific inhibitor of haematopoietic stem cell proliferation and some members of the C-X-C branch are neutrophil-targeted inflammatory agents. Here we report that the RANTES protein of the C-C class causes the selective migration of human blood monocytes and of T lymphocytes expressing the cell surface antigens CD4 and UCHL1. CD4+/UCHL1+T cells are thought to be prestimulated or primed helper T cells involved in memory T cell function. The preferential attraction of T-cell subsets by specific cytokines could in part explain how lymphocytes are targeted, and may provide insight into the workings of T cell memory.
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PMID:Selective attraction of monocytes and T lymphocytes of the memory phenotype by cytokine RANTES. 169 35

The platelet-derived growth factor-inducible gene JE was found to encode a 148-residue basic (pI = 10.4) secretory protein which shows striking similarity to the gene products of a family of small inducible genes (SIG), LD78, TCA3, IP10, 3-10C, 9E3/pCEF4, and gro/MGSA, and to several of the proteins secreted from platelet alpha-granules. Members of the SIG family have spatially conserved cysteine residues that vary in distance by only one amino acid residue as well as conserved proline residues at analogous sites. Hydrophilicity plots show alternating hydrophobic and hydrophilic domains which are similar for all members of the SIG family except IP10 and platelet factor 4, which show similarities to each other. The genomic organization of SIG family members is similar in the location of the splice junctions and the number of introns and exons, suggesting that they were derived from a common ancestor. The collective evidence suggests that a family of inducible cytokines, which are mitogenic or chemotactic, may act as intercellular coordinators of diverse responses designed to combat infection and promote the healing and regeneration of injured tissue.
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PMID:Platelet-derived growth factor-inducible gene JE is a member of a family of small inducible genes related to platelet factor 4. 291 Aug 58

Toxic oxygen free radicals are believed to play a role in the pathogenesis of a number of respiratory diseases. In particular, pulmonary emphysema may occur because of the oxidative impairment of alpha 1-proteinase inhibitor (alpha 1-PI). We report in vitro data on a new thiol agent, P 1507 [N-5-(thioxo-L-prolyl)-L-cysteine], obtained in a series of experiments designed in view of its therapeutic potential in these clinical conditions. We found that P 1507 at the concentration of 5 x 10(-6) M was able to almost fully abolish the PMA-triggered PMN-induced oxidative impairment of alpha 1-PI. Protection may be due to the radical scavenger ability of P 1507, that markedly reduced superoxide anion production from PMNs. We also found that P 1507 did not significantly impair other defence mechanisms of PMNs (i.e. phagocytosis, chemotaxis and bactericidal activity). The release of cytokines (TNF-alpha, IL-6 and IL-8) from monocytes was not altered in the presence of P 1507. We conclude that the compound P 1507 may be considered for treatment of clinical conditions characterized by overload of oxidants, on the basis of its ability in preventing the oxidative damage of alpha 1-PI and of a lack of unwanted inhibitory effects towards defence mechanisms of phagocytes.
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PMID:Interactions of P 1507, a new antioxidant agent, with phagocyte functions. 774 Oct 36

We have demonstrated that the orphan receptor representing the putative mouse (mu) homolog of the human (hu) interleukin-8 receptor beta (IL-8R beta) binds the mouse N51 cytokine, also known as KC. The muIL-8R beta gene was constitutively expressed in NIH 3T3 cells (NIH-muIL-8R beta). Cells and plasma membranes from the NIH-muIL-8R beta clone showed binding of 125I-N51 that was displaced by unlabeled N51. Other related cytokines were assayed for their ability to displace 125I-N51. MIP-2 and GRO alpha/MGSA competed as well as N51 for the receptor, but huIL-8 and NAP-2 did not compete at all. Chimeric molecules between IL-8 and N51 were used to extend the binding analysis. The segment between the conserved cysteines 2 and 3, named domain I; cysteines 3 and 4, domain II; and cysteine 4 and the C terminus, domain III of IL-8 were replaced by the corresponding domains of N51 and vice versa. When studying the binding of 125I-N51 and the hybrid molecules to the receptor, we observed that chimeras of N51 containing either domain I, II, or III of IL-8 were agonists of N51, and chimeras of IL-8 containing domain II or III of N51 were partial agonists of N51. These results demonstrate that domain I of N51 does not confer binding specificity and suggest that the region from the third cysteine to the C terminus of the N51 molecule is more important for binding to muIL-8R beta.
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PMID:The orphan mouse receptor interleukin (IL)-8R beta binds N51. Structure-function analysis using N51/IL-8 chimeric molecules. 789 Jun 4

Interleukin-8 (IL-8) is a potent chemotactic protein for polymorphonuclear leukocytes (PMN). Here we examine whether PMN synthesize and release IL-8 in response to stimulation by leukotriene B4 (LTB4). PMN isolated from normal heparinized peripheral human blood were incubated in RPMI culture medium at 37 degrees C in 5% CO2, with and without LTB4. The culture supernatants were tested for IL-8 bioactivity through chemotactic activity measurements with and without neutralizing anti-IL-8 serum. Immunoreactive IL-8 was quantified by ELISA, and de novo IL-8 synthesis was evaluated by metabolic labeling with [35S]cysteine followed by immunoprecipitation. LTB4 stimulated PMN to produce IL-8 in a dose- and time-dependent manner. The IL-8 concentrations reached maximal levels after 16 h of incubation with LTB4. Significant increases in IL-8 production occurred with LTB4 doses of 10 to 1,000 nM/ml. Immunoprecipitation of labeled IL-8 documented new synthesis of IL-8 by LTB4-treated PMN. Northern blot analysis of total RNA from PMN using a 30 mer oligonucleotide for IL-8 demonstrated increased mRNA expression in LTB4-stimulated PMN compared with untreated PMN. These data show that peripheral blood PMN can be stimulated by LTB4 to synthesize and secrete biologically active IL-8. PMN and other cells capable of producing LTB4 may induce IL-8 protein production by inflammatory PMN and thereby amplify or perpetuate the acute inflammatory response by recruiting additional PMN into an inflammatory site.
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PMID:Leukotriene B4 stimulates human polymorphonuclear leukocytes to synthesize and release interleukin-8 in vitro. 800 41

Plasmodium vivax and the related monkey malaria, P. knowlesi, require interaction with the Duffy blood group antigen, a receptor for a family of chemokines that includes interleukin 8, to invade human erythrocytes. One P. vivax and three P. knowlesi proteins that serve as erythrocyte binding ligands in such interactions share sequence homology. Expression of different regions of the P. vivax protein in COS7 cells identified a cysteine-rich domain that bound Duffy blood group-positive but not Duffy blood group-negative human erythrocytes. The homologous domain of the P. knowlesi proteins also bound erythrocytes, but had different specificities. The P. vivax and P. knowlesi binding domains lie in one of two regions of homology with the P. falciparum sialic acid binding protein, another erythrocyte binding ligand, indicating conservation of the domain for erythrocyte binding in evolutionarily distant malaria species. The binding domains of these malaria ligands represent potential vaccine candidates and targets for receptor-blockade therapy.
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PMID:Identification of the erythrocyte binding domains of Plasmodium vivax and Plasmodium knowlesi proteins involved in erythrocyte invasion. 804 29


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