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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 is the most extensively characterised member of the structurally related chemotactic and pro-inflammatory proteins collectively called chemokines. It binds to two closely related members of the seven transmembrane chemokine receptor family found on a variety of leukocyte cell types. In order to study the interaction of interleukin-8 with its receptors, and their distribution, we have produced a fluorescently labelled protein as an alternative to the radioactive 125I-interleukin-8 ligand. Interleukin-8 is naturally produced as two forms, a 72-residue polypeptide by monocytes and a 77-residue form produced by endothelial cells which has an extension of five amino acids at the amino terminal. Both forms are active at nanomolar concentrations, implying that chemical modification to the amino terminus of the 72-residue form will not destroy activity. The 72-residue interleukin-8 sequence starts with a serine residue, which can be oxidised under mild conditions to give a reactive glyoxylyl function which is then reacted with a nucleophilic fluorescein derivative. The site-specifically labelled protein was easily isolated by reverse-phase HPLC. The dissociation constant of the fluorescently labelled interleukin-8 from its receptors on neutrophils was measured by displacement of 125I-interleukin-8 and found to be 10 nM compared to 1 nM for the unmodified protein. The modified protein is highly active in in vitro bioassays using human neutrophils, giving an EC50 of 7 nM in chemotaxis and an EC50 of 0.62 nM for shape change. The binding of the fluorescent protein to neutrophils can also be measured by fluorescent automatic cell sorter (FACS) analysis, and can be competed by unlabelled interleukin-8. The amino-terminal modification of interleukin-8 has produced a reagent which is useful for the quantification of interleukin-8 receptor expression, and will also be useful in monitoring the fate of the ligand after receptor binding.
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PMID:A fluorescent interleukin-8 receptor probe produced by targetted labelling at the amino terminus. 785 4

Transforming growth factor (TGF)-alpha is a pleiotropic polypeptide which mediates a variety of tissue-specific cellular responses such as induction of proliferation, cell migration, vascularization, and formation of extracellular matrix. TGF-alpha is produced by certain tumor cells and embryogenic tissues, as well as by normal cells of different origin. Within the granulocytic lineage, TGF-alpha production has been shown in promyelocytic leukemia cells induced to differentiate, as well as in blood eosinophils of patients with the idiopathic hypereosinophilic syndrome. The present study was carried out in order to examine expression of the TGF-alpha gene in polymorphonuclear (PMN) and mononuclear (MN) blood cells of normal healthy donors. While MN and neutrophilic PMN failed to synthesize TGF-alpha transcripts and protein, eosinophils constitutively exhibited TGF-alpha transcripts accompanied by the release of immunoreactive TGF-alpha protein. Exposure of PMN and MN cells to the leukocyte-activating cytokines interleukin (IL)-3, IL-5, and granulocyte-macrophage colony-stimulating factor resulted in a several-fold increase of TGF-alpha mRNA expression and protein release by eosinophils, but not by neutrophils and MN cells. PMN and MN were insensitive to induction of TGF-alpha release by IL-8 and granulocyte colony-stimulating factor. These results point to a functional role of eosinophils in disorders characterized by unbalanced TGF-alpha production such as disease states associated with abnormal matrix formation and neovascularization which may be explained by the present demonstration of TGF-alpha production in these cells.
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PMID:Expression of the transforming growth factor-alpha gene by human eosinophils is regulated by interleukin-3, interleukin-5, and granulocyte-macrophage colony-stimulating factor. 812 34

We have identified, by differential cDNA library screening, 15 serum inducible genes in the human diploid fibroblast cell line WI-38. The genes fall into two classes that are distinguished by their dependence on protein synthesis for the induction by serum, i.e., primary and secondary genes. While 11 of these genes encode known proteins, 4 other genes have not been described to date. The former genes encode proteins of diverse functions, including the monocyte-derived neutrophil chemotactic factor (MONAP), calmodulin, tropomyosin, tenascin, collagenase, plasminogen activator inhibitor-2a, the 'sperm-specific' cleavage signal-1 protein, metallothionein IIa and the mitochondrial chaperonin hsp-60. Interestingly, one of the unknown genes contains a large open reading frame for a polypeptide that is highly homologous to a previously unidentified long open reading frame in the opposite strand of the gene coding for the transcription factor HTF-4. We also studied the regulation of these serum-induced genes during cell cycle progression in normally cycling WI-38 and HL-60 cells separated by counterflow elutriation as well as in serum-stimulated HL-60 cells. Our results clearly show that, in contrast to the prevailing opinion, the expression of most genes induced after mitogen stimulation is not subject to a significant regulation in normally proliferating cells. This supports the hypothesis that the progression into S from either G0 or G1 are distinct processes with specific patterns of gene expression.
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PMID:Identification of serum-inducible genes: different patterns of gene regulation during G0-->S and G1-->S progression. 800 57

Interleukin-8 (IL-8) and growth regulatory gene/melanoma growth stimulatory activity (GRO/MGSA) are small polypeptide molecules involved in the chemotactic response of certain cell types. Two receptors have been described which interact with IL-8, designated type 1 and type 2. IL-8 binds with high affinity to both receptors, whereas GRO/MGSA and neutrophil-activating peptide-2 demonstrate a high degree of binding only to the type 2 receptor. The two forms of IL-8 receptor are members of the rhodopsin seven-helix membrane-spanning superfamily, and share a high degree of overall homology, although the amino termini are very divergent. By using conserved restriction enzyme sites, a series of chimeric IL-8 receptor molecules were constructed between the type 1 and type 2 receptors and transfected into human 293 kidney epithelial cells. These chimeric molecules altered regions of the receptor presented to the ligand. The ability of the chimeric receptors to bind IL-8 was determined, as well as the ability of IL-8 and GRO/MGSA to inhibit radiolabeled IL-8 binding. The amino terminus of the IL-8 receptors was found to be important for differential binding of GRO/MGSA and IL-8. In addition, a series of peptides was also constructed to further investigate which residues of IL-8 receptor interact with IL-8. These peptides also identified the amino-terminal sequence of the IL-8 receptors as being important in interacting with IL-8.
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PMID:Importance of the amino terminus of the interleukin-8 receptor in ligand interactions. 846 64

Hyperplasia of mesangial cells (MCs) precedes or accompanies progressive glomerular scarring, as is seen in chronic glomerulonephritis and diabetic glomerulosclerosis. The mechanisms causing in vivo MC proliferation and production of extracellular matrix (ECM) are incompletely understood. Cell culture studies have demonstrated that MCs produce as well as react to various polypeptide cytokines. Thus, MCs have the potential to generate soluble mediators which can, in a paracrine fashion, attract and activate inflammatory cells (platelets, monocyte-macrophages, granulocytes), for example by IL-6, IL-8, MCP-1 and GM-CSF, and exert autocrine effects on MCs themselves, such as by promoting MC proliferation (by PDGF, IL-1, IL-6) or ECM production (by TGF-beta, IL-1). Recent in vitro results have revealed that specific non-soluble ECM components (collagen III, IV; laminin) also affect MC behavior with regard to adhesion, cell replication, ECM production as well as their response to cytokines. The latter effect appears to be mediated by alterations of cytokine receptor expression on MCs in the presence of the ECM components. "Cross-talk" between MCs, cytokines, ECM and inflammatory cells is likely to be of great importance in the regulation of the MC phenotype and may play a prominent role in the initiation and progression of glomerular inflammation. First in vivo findings in rats with experimental glomerular disease and in kidney biopsies from patients with glomerulonephritis have supported this concept by demonstrating abnormal MC expression of cytokines, their receptors and ECM proteins. These MC products may promote the recruitment and activation of inflammatory cells and perpetuate MC proliferation as well as ECM build-up.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokines and mesangial cells. 846 21

Glycosylation-inhibiting factor (GIF) is a cytokine that is involved in the regulation of IgE synthesis. The crystal structure of recombinant human GIF was determined by the multiple isomorphous replacement method. The structure was refined to an R factor of 0.168 at 1.9 angstrom resolution. The overall structure is seen to consist of three interconnected subunits forming a barrel with three 6-stranded beta-sheets on the inside and six alpha-helices on the outside. There is a 5-angstrom-diameter "hole" through the middle of the barrel. The barrel structure of GIF in part resembles other "trefoil" cytokines such as interleukin 1 and fibroblast growth factor. Each subunit has a new class of alpha + beta sandwich structure consisting of two beta-alpha-beta motifs. These beta-alpha-beta motifs are related by a pseudo-twofold axis and resemble both interleukin 8 and the peptide binding domain of major histocompatibility complex protein, although the topology of the polypeptide chain is quite different.
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PMID:The crystal structure of human glycosylation-inhibiting factor is a trimeric barrel with three 6-stranded beta-sheets. 861 Jan 59

Human or bovine lactoferrin (LF) and lactoferricin (LFcin), a peptide derived from the N-terminal region of LF, each have the ability to stimulate the release of neutrophil-activating polypeptide interleukin 8 (IL-8) from human polymorphonuclear leukocytes (neutrophils, PMNs). This finding suggests that LF and LFcin may both function as immunomediators for activating the host defense system. A basic peptide, protamine, exerted the same effect as that of LF and LFcin, suggesting the importance of the basic nature of LF and LFcin in acting as an inducer of IL-8 release from PMNs.
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PMID:Effects of lactoferrin and lactoferricin on the release of interleukin 8 from human polymorphonuclear leukocytes. 890 Nov 16

Secretory IgA, which plays an important role in the defense of the exocrine tissue, is composed of a polymeric IgA, joining (J) chain and secretory component (SC). Polymeric IgA and J chain are produced by plasma cells and SC by glandular epithelial cells. We here described the molecular aspects of J chain and SC. Study of the J chain has been confined to vertebrates which produce immunoglobulin (Ig) because the function of J chain is considered to be a polymerization of Ig. Recent molecular studies indicate that the role of J chain has been questioned. The J chain is expressed in invertebrates, as well as, representative species of vertebrates and that J chain is a primitive polypeptide that arose before the evolution of Ig molecules. SC is a 80 kDa glycoprotein functioning as a receptor for J chain-containing polymeric Ig. The expression of SC is regulated by various inflammatory cytokines such as, IL-1, IL-4, IL-6, IL-8, IFN-gamma and TNF-alpha, suggesting SC upregulation in vivo in inflammatory conditions. The human SC cDNA analysis reveals that it consisted of 11 exons with no functional TATA-box or CCAAT-box in the putative promoter region. Further upstream, there are several interesting motifs such as NF-kB and IFN-gamma response element, suggesting possible regulation of SC by cytokines through cellular signal transduction pathways.
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PMID:[Molecular aspects of secretory IgA (S-IgA) in gut-associated lymphoid tissues]. 892 Jun 90

Cytokines are a heterogenous group of polypeptide mediators that have been associated with activation of numerous functions, including the immune system and inflammatory responses. The cytokine families include, but are not limited to, interleukins (IL-I alpha, IL-I beta, ILIra and IL-2-IL-15), chemokines (IL-8/ NAP-I, NAP-2, MIP-I alpha and beta, MCAF/MCP-1, MGSA and RANTES), tumor necrosis factors (TNF-alpha and TNF-beta), interferons (INF-alpha, beta and gamma), colony stimulating factors (G-CSF, M-CSF, GM-CSF, IL-3 and some of the other ILs), growth factors (EGF, FGF, PDGF, TGF alpha, TGF beta and ECGF), neuropoietins (LIF, CNTF, OM and IL-6), and neurotrophins (BDNF, NGF, NT-3-NT-6 and GDNF). The neurotrophins represent a family of survival and differentiation factors that exert profound effects in the central and peripheral nervous system (PNS). The neurotrophins are currently under investigation as therapeutic agents for the treatment of neurodegenerative disorders and nerve injury either individually or in combination with other trophic factors such as ciliary neurotrophic factor (CNTF) or fibroblast growth factor (FGF). Responsiveness of neurons to a given neurotrophin is governed by the expression of two classes of cell surface receptor. For nerve growth factor (NGF), these are p75NTR (p75) and p140trk (referred to as trk or trkA), which binds both BDNF and neurotrophin (NT)-4/5, and trkC receptor, which binds only NT-3. After binding ligand, the neurotrophin-receptor complex is internalized and retrogradely transported in the axon to the soma. Both receptors undergo ligand-induced dimerization, which activates multiple signal transduction pathways. These include the ras-dependent pathway utilized by trk to mediate neurotrophin effects such as survival and differentiation. Indeed, cellular diversity in the nervous system evolves from the concerted processes of cell proliferation, differentiation, migration, survival, and synapse formation. Neural adhesion and extracellular matrix molecules have been shown to play crucial roles in axonal migration, guidance, and growth cone targeting. Proinflammatory cytokines, released by activated macrophages and monocytes during infection, can act on neural targets that control thermogenesis, behavior, and mood. In addition to induction of fever, cytokines induce other biological functions associated with the acute phase response, including hypophagia and sleep. Cytokine production has been detected within the central nervous system as a result of brain injury, following stab wound to the brain, during viral and bacterial infections (AIDS and meningitis), and in neurodegenerative processes (multiple sclerosis and Alzheimer's disease). Novel cytokine therapies, such as anticytokine antibodies or specific receptor antagonists acting on the cytokine network may provide an optimistic feature for treatment of multiple sclerosis and other diseases in which cytokines have been implicated.
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PMID:Neurotrophins and their receptors in nerve injury and repair. 910 50

Plasma levels of interleukin 12 (IL-12), a cytokine consisting of two different polypeptide subunits (p40 and p35), were measured together with interferon gamma (IFN-gamma) and other cytokines in 46 children with septic shock and purpura. The median (range) plasma IL-12 p40 level on admission was 457 (244-2677) pg/ml in non-survivors vs 189 (< 40-521) pg/ml in survivors (P = < 0.001). IL-12 p70 levels were elevated in only nine patients. IL-12 p40 plasma levels were positively correlated with tumour necrosis factor alpha (TNF-alpha), IL-6, IL-8, IL-10 and PRISM-score, whereas they were negatively correlated with C-reactive protein (CRP), whole blood cell (WBC) and serum glucose levels. Twelve (29%) of the patients had detectable levels of IFN-gamma. Thus, circulating levels of IL-12 p40 and to a lesser extent those of IL-12 p70, are elevated in children with septic shock and purpura, and correlate with severity of disease and outcome.
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PMID:Interleukin 12 levels during the initial phase of septic shock with purpura in children: relation to severity of disease. 932 21


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