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)

We developed a highly sensitive enzyme-linked immunosorbent assay (ELISA) for human monocyte chemotactic and activating factor (MCAF), an inflammatory cytokine that plays an important role in the recruitment of blood monocytes to areas of inflammation. The ELISA, which is based on a sandwich method using two newly-developed monoclonal antibodies, could quantitatively detect MCAF in the range between 2.5 pg/ml (50 fg/sample) to 300 pg/ml after incubation for a total of 2 h, and showed no cross-reactivity with various structurally-related IL-8 superfamily proteins. It was not affected by blood or urine components non-specifically, and thus was directly applicable to clinical specimens. When serum and urine samples from healthy subjects were measured, they all turned out to contain detectable levels of MCAF (more than 30 pg/ml). By gel-filtration column chromatography analysis, MCAF in the body fluids was eluted as a single peak at the position corresponding to the molecular weight of 10 kD, suggesting that it exists as a monomer form, free from carrier proteins. The established ELISA here is expected to be effectively used for the further investigations on the relationship of MCAF with various inflammatory diseases.
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PMID:Detection of monocyte chemotactic and activating factor (MCAF) in normal blood and urine using a sensitive ELISA. 800 31

Recent analysis of a various kinds of cytokines revealed that the cytokines are actively involved in a number of important biological functions including immunological and endocrine functions. The present study investigated the unique cytokine-mediated immunological and endocrinological functions in the intra-uterine space during pregnancy. A human placenta which expresses paternal and maternal antigens was revealed to escape from maternal immune systems by releasing immunosuppressive cytokines derived from the placenta. Placental cytokines such as interleukin-6 (IL-6) activated IL-6-receptor-mediated signal transduction pathways to produce human chorionic gonadotropin (hCG). IL-1 and tumor necrosis factor-alpha (TNF-alpha) synergistically augmented IL-6 production to stimulate hCG production. However, transforming growth factor-beta (TGF-beta) suppressed these cytokine-mediated hCG production as well as IL-6 production. Thus, these placental cytokines, mainly derived from trophoblasts, cooperatively contributed to hCG production. IL-8 and monocyte chemotactic and activating factor (MCAF) activate host defense mechanism by activating neutrophils and monocytes as well as macrophages, respectively. IL-6 also activates immune responses and promote synthesis of acute-phase reactant proteins, contributing to augmentation of host defense mechanism in a different way from IL-8 and MCAF. Human placenta in the 3rd trimester actively produced these cytokines for potentiation of placental defense mechanism during pregnancy and in chorioamnionitis. A fetus in chorioamnionitis also produced these cytokines in utero for potentiation of fetal defense mechanism. Among these cytokines, IL-8 in a cord serum was a very sensitive and useful marker for clinical diagnosis of chorioamnionitis. Cord serum IL-6, in contrast, stimulated the synthesis of surfactant protein-A (SP-A) to promote fetal lung maturation and reduce the incidence of RDS. Collectively, the present study revealed the cytokine network in the placenta regulating maternal immune responses, placental endocrine functions, feto-maternal defense mechanism and fetal respiratory maturation.
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PMID:[Immunological analysis of the mechanism of maternal tolerance of a fetus and the cytokine-mediated regulation of feto-placental functions]. 808 6

In order to elucidate the role of inflammatory cytokines in the central nervous system, we examined the production of two leukocyte chemoattractants, IL-8 and monocyte chemotactic and activating factor (MCAF) in brain tumor cell lines. The glioma cell lines tested exhibited high levels of IL-8 and MCAF mRNA expression upon stimulation with IL-1 or TNF-alpha, while none of the neuroblastoma cell lines expressed these cytokine mRNA. Both IL-8 and MCAF mRNA expression depended on the dose of IL-1 alpha and TNF-alpha and appeared very rapidly, reaching maximal levels at 3-6 hr, with substantial production of these cytokines in the culture supernatants. When various immunosuppressive drugs were tested, glucocorticoids but not other immunosuppressive drugs markedly inhibited the IL-1 or TNF-alpha-induced IL-8 and MCAF mRNA accumulation, suggesting that glucocorticoid is a potent regulator of these inflammatory cytokine production in the neural tissues. In addition, reverse transcription-polymerase chain reaction (RT-PCR) revealed the expression of IL-8 and MCAF mRNA expression in resected brain tumor tissues including glioblastoma, astrocytoma grade 2, ependymoma and medulloblastoma, indicating that these inflammatory cytokines are expressed in vivo.
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PMID:Induction and regulation of IL-8 and MCAF production in human brain tumor cell lines and brain tumor tissues. 811 36

A significant proportion of the infiltrating cells in several inflammatory skin diseases, including psoriasis and allergic contact dermatitis, are monocytes. Additionally, it is known that the cytokine monocyte chemotactic and activating factor (MCAF) can be produced by several cell types present in the skin, suggesting a significant role for MCAF in the accumulation of monocytes during immunological and inflammatory skin reactions. We have recently developed a precise method for quantification of the amount of a specific mRNA species in a given sample and have used this technique to compare specific MCAF mRNA amounts in cultures of human keratinocytes, dermal fibroblasts, endothelial cells, and monocytes, after stimulation with interleukin 1 alpha (IL-1 alpha) for 6 h. Endothelial cells produced very high, monocytes and fibroblasts intermediate, and keratinocytes low amounts of MCAF mRNA. We have also performed time course studies of MCAF mRNA levels in the four cell types. Our findings suggest that the regulation of MCAF mRNA expression in these cells parallels the regulation of the lymphocyte and neutrophil chemotactic factor interleukin 8.
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PMID:Expression of monocyte chemotactic and activating factor (MCAF) in skin related cells. A comparative study. 814 9

A mouse cDNA library was screened using a DNA fragment generated by polymerase chain reaction (PCR) with oligodeoxyribonucleotide primers which were derived from the conserved sequences in cDNAs encoding the human and rabbit interleukin-8 receptors (hIL-8R and rIL-8R). A novel cDNA was obtained encoding 359 amino acids (aa) with seven putative transmembrane portions similar to hIL-8R and rIL-8R. Its aa sequence shows 64 and 69% homology to those of type-1 and type-2 hIL-8R, respectively. COS-7 cells transfected with the isolated cDNA in a mammalian expression vector bind IL-8, but do not bind a related protein, monocyte chemotactic and activating factor, suggesting that the isolated cDNA encodes the mouse homolog of IL-8R. Northern blot analysis showed that mRNA of this clone was highly expressed in mouse peritoneal neutrophils, and the single band was observed in Southern blotting analysis on mouse genomic DNA digested with HindIII or KpnI, suggesting that this is a single-copy gene.
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PMID:Cloning of a cDNA encoding a mouse homolog of the interleukin-8 receptor. 819 68

Monocyte chemotactic and activating factor (MCAF) is an important mediator of monocyte recruitment to sites of chronic inflammation and neoplasia. In the present study, we determined whether MCAF can also enhance the activation of tumoricidal capacity of monocytes. Human monocytes incubated with MCAF and subthreshold concentrations of lipopolysaccharide (LPS) exhibited synergistic tumoricidal activity against allogeneic A375 melanoma cells, irrespective of their metastatic potential. The sequence of MCAF and LPS treatment was crucial. Monocytes treated first with MCAF for 4 h and then with LPS for 18 h were highly cytotoxic to the melanoma cells, whereas monocytes first treated with LPS and then with MCAF were not. Treatment of monocytes with MCAF and LPS also significantly increased production of tumor necrosis factor. These data suggest that like interferon-gamma, MCAF can prime human monocytes to respond to LPS. Interleukin-8, a chemokine for neutrophils, did not enhance the monocytes' LPS-triggered tumoricidal response. Collectively, these data show that MCAF can influence the recruitment and tumoricidal activation of blood monocytes. Therefore, MCAF may be an important mediator of tumor regression.
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PMID:Synergism between human recombinant monocyte chemotactic and activating factor and lipopolysaccharide for activation of antitumor properties in human blood monocytes. 826 May 37

Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE), a new biologic response modifier, was designed to target the immunomodulator to monocytes and macrophages. Human monocytes/macrophages phagocytize L-MTP-PE, with subsequent upregulation of interleukin (IL)-1 alpha, IL-1 beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, and monocyte chemotactic and activating factor genes and with the production and secretion of these cytokines in vitro. L-MTP-PE-activated macrophages kill tumor but not normal cells in vitro. Following i.v. infusion of L-MTP-PE into cancer patients, its uptake was demonstrated in liver, spleen, lung, and in and around metastases to lung. We also investigated whether L-MTP-PE therapy administered in a neoadjuvant setting could improve the disease-free interval in relapsed osteosarcoma patients with lung metastasis. Patients received either a 12- or 24-week course of L-MTP-PE after surgical removal of all metastases. Following L-MTP-PE infusion, induction of circulating TNF-alpha, IL-6, neopterin, and C-reactive protein was demonstrated. Disease-free intervals were calculated from the day of surgery to the day of relapse in each group and were compared with the disease-free interval for a historical control group. Those patients receiving 24 weeks of L-MTP-PE showed a significant (p < 0.03) prolongation in time to relapse. These data indicate that L-MTP-PE is an active agent against osteosarcoma and warrants further investigation in an adjuvant setting.
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PMID:Liposome-encapsulated MTP-PE: a novel biologic agent for cancer therapy. 828 Jul 10

In order to establish the pathophysiological roles of IL-8, rabbit IL-8 was expressed in Escherichia coli and purified to homogeneity by sequential chromatography on heparin agarose, CM-HPLC, and RP-HPLC. The purified recombinant rabbit IL-8 was homogeneous on SDS-PAGE and the ED50 of neutrophil chemotactic activity for rabbit peritoneal neutrophils was 2 ng/ml. The binding of 125I-labeled rabbit IL-8 to rabbit neutrophils was inhibited by unlabeled human IL-8 as well as rabbit IL-8 but not by another leucocyte chemotactic cytokine (chemokine), monocyte chemotactic and activating factor. Scatchard plot analysis of the binding of 125I-labeled rabbit IL-8 to rabbit peritoneal neutrophils revealed that the rabbit neutrophils have two affinity classes of receptors for IL-8 (Kd = 2.3 nM, 4.1 x 10(4) sites/cell; Kd = 18.0 nM, 11.4 x 10(4) sites/cell). It was found that a previously generated mouse anti-human IL-8 mAb, WS-4, inhibited the binding of 125I-labeled rabbit IL-8 to rabbit neutrophils, and blocked neutrophil chemotaxis in vitro in a specific and dose-dependent manner. An ELISA system for rabbit IL-8 was established using this mAb and guinea pig polyclonal antibodies to recombinant rabbit IL-8 to measure the levels of IL-8 in rabbit plasma. Intravenous administration of lipopolysaccharide (LPS) (100 micrograms) in rabbits caused the highest level of IL-8 in blood at around 2 h. Intravenous administration of WS-4 (10 mg) inhibited neutrophil infiltration at the site of LPS injection into the rabbit skin, suggesting that IL-8 is essential in the recruitment of neutrophils at sites of acute inflammation in vivo.
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PMID:Expression of recombinant rabbit IL-8 in Escherichia coli and establishment of the essential involvement of IL-8 in recruiting neutrophils into lipopolysaccharide-induced inflammatory site of rabbit skin. 834 59

Monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 (MCAF/MCP-1), RANTES, and macrophage inflammatory protein (MIP)-1 alpha are chemokines known to activate basophils (MCAF/RANTES) and eosinophils (RANTES/MIP-1 alpha). IL-8 inhibits MCAF-induced histamine release from basophils. We questioned whether a relationship exists between the levels of these chemokines and various inflammatory mediators released from mast cells, eosinophils, and basophils as assessed in nasal secretions obtained from patients during the allergy season and out of season. Samples were assessed for MCAF/MCP-1, RANTES, MIP-1 alpha, IL-8, histamine, tryptase and eosinophil cationic protein (ECP) in three subject groups: subjects with allergic rhinitis (n = 18), atopic subjects without rhinitis (n = 9), and healthy individuals (n = 6). Statistically significant differences were apparent only in the subjects with symptoms as follows. MCAF/MCP-1 increased during the season from 336 +/- 47 pg/ml to 829 +/- 137 pg/ml (p < 0.001), whereas IL-8 decreased from a baseline of 1932 +/- 335 pg/ml to 1070 +/- 202 pg/ml (p < 0.028). The ratio of IL-8 to MCAF/MCP-1 decreased during the symptomatic season from the baseline of 6.66 +/- 1.06 seen during winter to 1.3 +/- 0.22 during ragweed season (p < 0.001). Histamine increased from 6.3 +/- 1.5 to 89 +/- 15.5 ng/ml (p < 0.001), ECP increased from 20.6 +/- 6.4 to 237.1 +/- 50.2 ng/ml (p < 0.001), and tryptase increased from 2.34 +/- 0.6 to 9.7 +/- 2.3 U/ml (p < 0.001). Most samples did not have detectable quantities of MIP-1 alpha or RANTES. We also found a correlation between the level of MCAF/MCP-1 and IL-8 and the level of histamine or IL-8 and ECP. Our results suggest that the chemokines MCAF/MCP-1 and IL-8 may participate in the pathogenesis of allergic rhinitis, contributing to the attraction of the proinflammatory cells and mediator release, which might be very important during the late phase of the allergic reaction. Furthermore, the ratio of certain chemokines, such as MCAF/MCP-1 and IL-8 may reflect the magnitude of the reaction, as does the presence of histamine and ECP.
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PMID:Chemokines in seasonal allergic rhinitis. 856 22

The effect of inflammatory mediators on the expression of several surface adhesion molecules on the human mast-cell line (HMC)-1 was studied. By flow cytometry, it could be shown that among several surface adhesion molecules (ICAM-1/CD54, VLA-4/CD49d, Mac-1/CD11b, LFA-1/CD11a, LFA-2/CD2, LFA-3/CD58, VCAM-1), only the constitutively expressed immunoglobulin family member intercellular adhesion molecule-1 (ICAM-1) is modulated by proinflammatory cytokines on HMC-1 mast cells. Stimulation with tumor necrosis factor-a (TNF-alpha) and interferon-gamma (IFN-gamma) resulted, in addition to interleukin-(IL-)4, in selective upregulation of ICAM-1 expression. Costimulation of either IL-4 or IFN-gamma with TNF-alpha further increased the ICAM-1 expression as compared to the stimuli alone. In contrast, stem-cell factor (SCF), granulocyte/macrophage colony-stimulating factor (GM-CSF), IL-10, IL-8, monocyte chemotactic and activating factor (MCAF), and the complement split product C5a failed to modulate the expression of any adhesion molecule examined. The levels of cytoplasmic free calcium in HMC-1 mast cells were not altered by cross-linking surface ICAM-1, suggesting linkage of other intracellular signaling pathways. This cytokine-induced upregulation of ICAM-1 expression might reveal a putative regulatory mechanism of mast-cell interaction with effector cells bearing the counterparts of ICAM-1 (CD54), the molecules Mac-1 (CD11b/CD18) and leukosialin (CD43), and the principal ligand LFA-1 (CD11a/CD18).
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PMID:Modulation of intercellular adhesion molecule 1 (ICAM-1) expression on the human mast-cell line (HMC)-1 by inflammatory mediators. 890 94


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