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)

Two receptors for interleukin 8 (IL-8), IL-8rA and IL-8rB, have been cloned. Previous studies of neutrophils indicated that the two C-X-C chemokines, IL-8 and NAP-2, bind to IL-8rB with high affinity but that only IL-8 binds to IL-8rA with high affinity. In this study, human kidney embryonal 293 cells were transfected to express solely IL-8rA or IL-8rB (the cells are designated IL-8rA/293 and IL-8rB/293, respectively). The authors show that NAP-2 bound both IL-8rA and IL-9rB specifically. While NAP-2 and IL-8 bound IL-8rB with comparable high affinity (2.9 +/- 0.5 and 2.8 +/- 0.8 nM, respectively), NAP-2 showed a lower binding affinity to IL-8rA (9 +/- 2 nM) compared with IL-8 (1.3 +/- 0.5 nM). A lower number of binding sites was detected for NAP-2 than for IL-8 on IL-8rA/293 cells as well on IL-8rB/293 cells. On both cell types (IL-8rA/293 and IL-8rb/293), NAP-2 and IL-8 could completely inhibit [125I]NAP-2 binding, while unlabelled NAP-2 could only partially compete for [125I]IL-8 binding. Functional assays revealed that although NAP-2 is chemotactic for both IL-8rA/293 and IL-8rB/293 cells, it is less potent than IL-8. While NAP-2 induced chemotaxis of IL-8rB/293 cells at the same optimal concentrations as IL-8 (10-100 ng/ml), the induction of optimal migratory response of IL-8rA/293 cells required much higher concentrations of NAP-2 than IL-8 (1000-3000 ng/ml and 10-100 ng/ml, respectively). The dose-response curve of the IL-8rB/293 cells to IL-8 was bell shaped, while the response to NAP-2 was sustained at a plateau level even at concentrations as high as 3000 ng/ml. It is likely that tertiary structural differences between NAP-2 and IL-8 account for their divergent abilities to bind and chemoattract 293 cells transfected with either IL-8 receptor type A or type B.
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PMID:IL-8 and NAP-2 differ in their capacities to bind and chemoattract 293 cells transfected with either IL-8 receptor type A or type B. 906 94

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

This study was undertaken to define the regions of the human interleukin-8 type B receptor (IL8RB) which are critical for binding the ligands interleukin-8, NAP-2 and GRO alpha. Peptides corresponding to the N-terminus region and the first extracellular loop of the receptor demonstrated statistically significant (p = 0.001) inhibition of IL-8 control binding levels (inhibition levels of 73.0 +/- 5.1% and 89.9 +/- 2.2% respectively). In contrast, NAP-2 binding was inhibited only by the peptide representing the first extracellular loop (63.2 +/- 2.3%), while GRO alpha binding was inhibited by portions of the N-terminus (49.7 +/- 14.9% and 41.8 +/- 14.9%), but not the first extracellular loop. We suggest that: a) the chemokine receptor IL8RB, known to bind three related ligands with high affinity, seems to do so via distinct contact points and b.) the first extracellular loop is significant in the binding event.
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PMID:Mapping of the extracellular binding regions of the human interleukin-8 type B receptor. 912 32

All 12 of the human CXC chemokine genes were physically mapped using gene-specific PCR primers and the GenBridge 4 radiation hybrid panel. Nine genes, PF4, PF4V1, GRO1, GCP2, PPBP, IL8, GRO2, GRO3, and SCYB5, were assigned within a 1.8-cR interval of one another on 4q. Two additional genes, MIG and INP10, map within 0.5 cR of each another and 6 cR distal to the above-mentioned group. The final gene, SDF1, is localized on 10q. Phylogenetic analyses of amino acid sequences revealed that SDF1 is the most divergent member and that the physically separated MIG-INP10 pair constitutes a distinct evolutionary lineage.
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PMID:Localization of the human CXC chemokine subfamily on the long arm of chromosome 4 using radiation hybrids. 946 7

The solution structure of murine macrophage inflammatory protein-2 (MIP-2), a heparin-binding chemokine that is secreted in response to inflammatory stimuli, has been determined using two-dimensional homonuclear and heteronuclear NMR spectroscopy. Structure calculations were carried out by means of torsion-angle molecular dynamics using the program X-PLOR. The structure is based on a total of 2390 experimental restraints, comprising 2246 NOE-derived distance restraints, 44 distance restraints for 22 hydrogen bonds, and 100 torsion angle restraints. The structure is well-defined, with the backbone (N, Calpha, C) and heavy atom atomic rms distribution about the mean coordinates for residues 9-69 of the dimer being 0.57 +/- 0.16 A and 0.96 +/- 0.12 A, respectively. The N- and C-terminal residues (1-8 and 70-73, respectively) are disordered. The overall structure of the MIP-2 dimer is similar to that reported previously for the NMR structures of MGSA and IL-8 and consists of a six-stranded antiparallel beta-sheet (residue 25-29, 39-44, and 48-52) packed against two C-terminal antiparallel alpha-helices. A best fit superposition of the NMR structure of MIP-2 on the structures of MGSA, NAP-2, and the NMR and X-ray structures of IL-8 are 1.11, 1.02, 1.27, and 1.19 A, respectively, for the monomers, and 1.28, 1.10, 1.55, and 1.36 A, respectively, for the dimers (IL-8 residues 7-14 and 16-67, NAP-2 residues 25-84). At the tertiary level, the main differences between the MIP-2 solution structure and the IL-8, MGSA, and NAP-2 structures involve the N-terminal loop between residues 9-23 and the loops formed by residues 30-38 and residues 53-58. At the quaternary level, the difference between MIP-2 and IL-8, MGSA, or NAP-2 results from differing interhelical angles and separations.
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PMID:Solution structure of murine macrophage inflammatory protein-2. 962 82

Chemokines consist of a family of 8-16-kDa cytokines that are generated very early in a wide variety of inflammatory responses and attract leukocytes to local sites. At nanomolar concentrations chemokines initiate signal transduction and activate leukocytes through seven transmembrane receptors (STM), but higher micromolar doses result in homologous desensitizing effects. On the basis of reports that opiates have anti-inflammatory effects and also use STM, we have investigated the possibility that they may cross-desensitize the response of leukocytes to chemokines. We have confirmed previous observations that met-enkephalin (MET) is chemotactic for human peripheral blood monocytes. Furthermore, we observed that preincubation of monocytes or neutrophils with MET or morphine prevented their subsequent chemotaxis in response to chemokines (MIP1 alpha or IL-8). However, MET did not inhibit the chemotactic response of PMN to NAP-2, a homologous chemokine that is less potent than IL-8 but cannot be desensitized. The inhibitory effect of opiates on chemokine-induced chemotaxis was antagonized by naloxone. Since MIP-1 alpha and IL-8, unlike NAP-2, have the capacity to desensitize leukocytes, it is possible that opiates, by desensitizing some chemokine responses, can suppress inflammatory reactions.
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PMID:Opiate inhibition of chemokine-induced chemotaxis. 962 32

The purpose of this study was to compare blood cell activation during in vitro long-term perfusion using 2 parallel in vitro extracorporeal membrane oxygenation (ECMO) systems. We compared two substantially different perfusion systems, an assistance respiratoire extra corporelle (AREC) system on one hand, containing an AREC pump, silicon tubing, and a hollow-fiber oxygenator, and a centrifugal pump system, on the other hand, containing a Biomedicus centrifugal pump, PVC tubing, and a membrane oxygenator. We measured the platelet count using an automated blood cell counter. Platelet activation was evaluated using a flow cytometric technique for the platelet membrane expression of glycoproteins and ELISA for the plasma concentration of beta-thromboglobulin (beta-TG), a platelet specific protein released into the blood upon platelet activation. The neutrophil count was assayed using an automated blood cell counter and the plasma concentration of cytokines using an ELISA kit. A significant difference between the two systems was observed in terms of the platelet membrane expression of glycoprotein (GP)Ib (p=0.0001) and GPIIb/IIIa (p=0.0037), indicating a lower degree of platelet activation in the AREC system. The concentration of neutrophils was significantly lower in the centrifugal system (p=0.002) compared to the AREC system. The neutrophil membrane expression of CD11b was significantly lower (p=0.0067) in the AREC system, indicating a lower degree of neutrophil activation compared to the centrifugal pump system. A significantly lower degree of hemolysis, as expressed by plasma hemoglobin, was observed in the AREC pump system (p=0.0491). In conclusion, lower degrees of the platelet membrane expression of GPIb and GPIIb/IIIa and of the neutrophil membrane expression of CD11b were observed in the AREC system, indicating a lower degree of platelet and neutrophil activation in this system. No significant difference between the two systems as to the plasma concentration of interleukin (IL)-1beta, IL-6, or IL-8 could be recorded. Further studies are warranted to specify the role of each individual component of the two systems.
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PMID:Induced cell trauma during in vitro perfusion: a comparison between two different perfusion systems. 987 97

Heparin-induced thrombocytopenia (HIT) is a drug induced immunohematologic adverse reaction which is a rare but potentially very severe accident. Its diagnosis is important for epidemiologic and drug surveillance studies and in order to decide the most appropriate treatment. Its importance is enhanced since there is no gold standard diagnostic criteria. In clinical practice the diagnosis is based on a group of criteria related to clinical events and laboratory tests. We have established a score based on anamnestic criteria which allowed us to evaluate and compare two different laboratory tests: a platelet aggregation test (PAT) and a test for the detection of heparin dependent antibodies (Heparin Platelet Induced Antibodies or HPIA). The functional test PAT which is commonly used in expert laboratories detects antibodies inducing platelet aggregation in the presence of heparin. The HPIA test more recently developed is an ELISA test which detects antibodies directed at heparin-platelet factor 4 complexes. The relative value of theses two methods for the diagnosis of HIT is not well documented. We have analysed the results of these two tests in 273 consecutive patients with a suspicion of HIT. The results were concordant in 70% of patients. In selecting the patients with the lowest and the highest probability of HIT according to the score, PAT was found a more sensitive and HPIA a more specific test than the other. At low probability PAT is more often positive than HPIA 18% and 9% respectively. No test is 100% reliable, the specificity being limited for both tests since in about 20% of cases one or both tests are negative contrasting with a highly probable HIT. In this last group of patients, PAT was more frequently positive (86%) than HPIA (72%). Both tests are negative in 6% of patients suggesting the existence of presently unknown antigenic targets. Considering a group of 19 patients with a high probability of HIT, we have found antibodies against IL-8 or NAP-2 in only 7 patients. The discrepancy between a HPIA positive and a PAT negative encountered in 8% of patients may be explained by the existence of IgA or IgM immunoglobulins since in contrast to IgG they are unable to promote platelet aggregation via the CD32 platelet membrane receptor. This work suggests than neither test is 100% reliable and that they play a complementary role in the diagnosis of HIT. The potential advantage of using both tests should be confirmed in complementary studies
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PMID:[Heparin-induced thrombopenia: significance and difficulties of precise identification of the immunologic mechanism]. 991 45

A physical map of the CXC chemokine locus on chromosome 4 has been constructed by PCR analysis and PFGE mapping of YAC clones. The genes for IL8, GRO1, PPBP, PF4, SCYB5 (ENA-78) and SCYB6 (GCP-2) have been co-localized on a 335-kb genomic fragment. The GRO2 and GRO3 genes did not map within this region and based on analysis of a YAC contig overlapping IL8 we speculate that GRO2 and GRO3 map downstream of this region. We have also assigned the novel CXC chemokine gene, SCYB9B (alias H174/betaR1) to chromosome 4q21, upstream and within 12 kb of INP10. Like INP10 and MIG, INP10 and SCYB9B are arranged in a head to tail manner. The chromosomal arrangement of these genes appears to reflect the evolution of this multigene family and supports the theory that it arose by gene duplication.
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PMID:Physical mapping of the CXC chemokine locus on human chromosome 4. 1034 98

To clarify the roles of megakaryocytes and platelets in the responses associated with infection and inflammation, we examined the effects of interleukin (IL) 1, the common mediator of the inflammatory process, on the development and secretory functions of megakaryocytes generated from CD34(+)cord blood cells under stimulation with thrombopoietin (TPO). The addition of IL-1alpha did not influence the generation, endomitosis or expression of surface makers of megakaryocytes, compared with TPO alone. However, IL-1alphaenhanced the ability of megakaryocytes to produce IL-8 and growth-regulating oncogene-alpha(GRO-alpha) in the presence of TPO. In contrast, the production of regulated on activation with normal T cell expressed and secreted (RANTES), platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG) were not potentiated. A flow cytometric analysis and a reverse transcription-polymerase chain reaction analysis revealed IL-1 receptor type I (IL-1RI) expression of megakaryocytes generated by TPO. Moreover, the addition of an anti-IL-1RI monoclonal antibody significantly decreased the TPO plus IL-1alpha-induced secretion of IL-8 by the cultured megakaryocytes to the level attained by TPO alone. These results suggest that the production of IL-8 and GRO-alpha (but not RANTES), PF4 and beta-TG, by megakaryocytes is potentiated by signalling through IL-1RI with the aid of TPO. Thus, megakaryocytes and platelets may play an important role in the development of inflammation via chemokine release.
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PMID:Chemokine production by human megakaryocytes derived from CD34-positive cord blood cells. 1034 82

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