Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent cloning of human and murine IL-1 receptor (IL-1R) has revealed that there are at least two type of IL-1R: type I IL-1R is detected on T cells and fibroblasts and consists of 552 AAs with a cytoplasmic domain of 213 AAs, while type II is detected on B cells and monocytic cell lines and consists of 398 AAs with a short stretch intracytoplasmic domain of 29 AAs. Extracytoplasmic portion of IL-1R has some homology with vaccinia virus B15 Ag or fibroblast protein ST-2, while cytoplasmic portion has considerable similarity with Drosophila toll gene. By transfecting murine type I IL-1R cDNA into a human Jurkat cell line, structural and functional potion required for the IL-1 signal transduction is determined. At least broad portion of cytoplasmic domain including 364-474 AAs from N-terminus are found to be essential, while PKC acceptor site (Ser-431 and Ser-509), and PKA acceptor site (Ser-528) are not essential for the IL-8 gene expression.
 ...
PMID:[Function, molecular structure and gene expression of interleukin-1]. 143 66

Interleukin-8 (IL-8) such as LUCT (lung giant cell carcinoma-derived chemotactic protein), NAP (neutrophil activating protein) and MDNCF (monocyte-derived neutrophil chemotactic factor), and formylmethionyl-leucyl-phenylalanine (fMLP) are well-known chemoattractants for human polymorphonuclear leukocytes (PMNs) and are able to stimulate phosphorylation of 64-kd protein (p64) in these leukocytes. To elucidate the molecular mechanism of PMN activation with chemoattractants, we investigated the phosphorylation process of p64 in an intact cell. 32P-Labeled PMNs were stimulated with LUCT/IL-8, fMLP, leukotriene B4, or C5a, and phosphorylated proteins were analyzed by two-dimensional electrophoresis and autoradiography. A marked phosphorylation of p64 was observed after stimulation. A new spot of phosphorylated p64 (pp64) could be detected on the gel stained with Coomassie Brilliant Blue, indicating that the isoelectric point (pI) of p64 shifted from 5.3 to a more acidic pI by the phosphorylation forming pp64. The spot of pp64 was shown to be dephosphorylated to p64 by treatment with calf intestine alkaline phosphatase. Other proteins having molecular masses 82, 66, 58, 55 and 50 kd were also phosphorylated. The fMLP-stimulated phosphorylation was time-dependent and saturated within 5 min. Maximum stimulation was achieved with 10 nM fMLP. Phosphoamino acid analysis revealed phosphorylation of serine residues in pp64. Staurosporine (100 nM) and W-7 (100 microM) significantly inhibited the phosphorylation of p64, but H-7 slightly inhibited it. H-8 and herbimycin A did not effect phosphorylation. Phorbol myristate acetate was found to stimulate significantly. Protein kinase C did not stimulate the phosphorylation. These data suggest that protein kinase C and calmodulin-like protein are indirectly involved in the phosphorylation of p64 during chemoattractant-activation of PMN.
 ...
PMID:Characterization of a 64-kd protein phosphorylated during chemotactic activation with IL-8 and fMLP of human polymorphonuclear leukocytes. I. Phosphorylation of a 64-kd protein and other proteins. 839 62

Production of interleukin 8 (IL-8) is believed to be important in the pathogenesis of the gastritis seen in Helicobacter pylori infection. The aim of this study was to investigate the roles of protein kinase A (PKA), protein kinase C (PKC), protein tyrosine kinase (PTK) and intracellular calcium in the induction of IL-8 production by gastric epithelial cells. AGS gastric epithelial cells were stimulated with H. pylori, tumour necrosis factor alpha or interleukin 1beta together with activators or inhibitors of the relevant kinases. IL-8 production was measured by enzyme-linked immunosorbent assay. Helicobacter pylori, tumour necrosis factor alpha and interleukin 1beta produced a dose-dependent increase in IL-8 production. The increase with all three was significantly reduced by the tyrosine kinase inhibitors herbimycin A and genistein. Activation of PKC by phorbol myristate acetate was also an effective stimulus to IL-8 production and this was blocked by PKC depletion or inhibitors. Protein kinase C inhibition did not reduce the stimulation produced by H. pylori or the cytokines. Stimulation of PKA with forskolin or dibutyryl cyclic adenosine monophosphate or inhibition with H89 had no effect on IL-8 production. The calcium ionophore A23187 was a weak, PKC dependent, stimulant of IL-8 production. The production of IL-8 in AGS cells is stimulated via tyrosine kinase and protein kinase C dependent pathways. Stimulation by H. pylori, tumour necrosis factor alpha and interleukin 1beta requires tyrosine kinase activity.
 ...
PMID:Stimulation of IL-8 production in human gastric epithelial cells by Helicobacter pylori, IL-1beta and TNF-alpha requires tyrosine kinase activity, but not protein kinase C. 923 14

Leukaemia inhibitory factor (LIF) acts on the growth and differentiation of haematopoietic cells. By using a specific enzyme-linked immunosorbent assay for human LIF, we demonstrate that human bone marrow stromal cells produce LIF. LIF synthesis is enhanced in a dose-dependent manner after stimulation with lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMAS). LIF production in response to PMA is PKC-dependent since the two PKC inhibitors sphingosine and staurosporine markedly diminished it. Interleukin 1alpha (IL-1alpha), IL-1beta, IL-3, IL-6, IL-8, tumour necrosis factor (TNF-alpha) and SCF (both at 10 ng/ml) stimulate LIF production. By contrast macrophage colony-stimulating factor (M-CSF), granulocyte (G)-CSF, GM-CSF, basic fibroblast growth factor (bFGF), platelet-activating factor (PAF), protaglandin E2 (PGE2), leukotriene B4 (LTB4), and leukotriene C4 (LTC4) did not. These results suggest that bone marrow stromal cells might represent a major source for the cytokine-regulated local production of LIF inside human bone marrow.
 ...
PMID:Spontaneous and inducible production of leukaemia inhibitory factor by human bone marrow stromal cells. 934 7

In previous studies, we reported that sphingosine 1-phosphate (Sph-1-P) inhibits the chemotactic motility of some cancer cell lines such as mouse melanoma cells, as well as human smooth muscle cells, at a very low concentration, as demonstrated by a transwell migration assay method (Proc. Natl. Acad. Sci. USA 89, 9698, 1992; J. Cell Biol. 130, 193, 1995). In this study, we investigated the effect of Sph-1-P on the chemotactic motility and invasiveness of human neutrophils, utilizing three different assay systems: (a) a transwell migration assay where IL-8 or fLMP was added as a chemotactic factor, (b) a phagokinetic assay with gold colloids, and (c) a trans-endothelial migration assay with human umbilical vein endothelial cells (HUVECs) plated on collagen layers. We found that among various sphingosine derivatives, Sph-1-P specifically inhibited the IL-8- or fLMP-induced chemotactic migration of neutrophils at concentrations below 1 microM. Phagokinetic activity of neutrophils was also suppressed by Sph-1-P, but more moderately than by the PKC inhibitory sphingosine analog, trimethylsphingosine. Finally, Sph-1-P inhibited trans-endothelial migration and invasiveness of neutrophils into HUVEC-covered collagen layers, whereas no effect on their adhesion to HUVECs was observed. These observations strongly suggest that Sph-1-P can act as a specific and effective motility regulator of human neutrophils, raising the possibility of future applications of Sph-1-P, or its analogs, as anti-inflammatory agents regulating invasive migration of neutrophils through endothelial layers at injured vascular sites.
 ...
PMID:Inhibition of chemotactic motility and trans-endothelial migration of human neutrophils by sphingosine 1-phosphate. 945 9

By using a specific enzyme-linked immunosorbent assay, the authors demonstrated that human bone marrow stromal cells produce IL-6 and IL-8. Their synthesis is enhanced in a dose-dependent manner after stimulation with lipopolysaccharide (LPS) and phorbol myristate acetate (PMA). Interleukin 6 (IL-6) and IL-8 production in response to PMA were markedly diminished by the PKC inhibitor staurosporine. IL-6 (10 ng/ml) stimulated IL-8 production with 0% and 10% fetal calf serum (FCS) in the culture medium. In similar conditions, IL-8 (10 ng/ml) enhanced IL-6 production. IL-1 alpha, IL-1 beta, and IL-3, tumour necrosis factor alpha (TNF-alpha), Stem cell factor (SCF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (at 10 ng/ml) stimulated IL-6 and IL-8 production in 0% and 10% FCS. G-CSF stimulated and IL-4 inhibited IL-8 production in 10% FCS. IL-2, IL-4 and bFGF stimulated IL-6 production in 0% FCS. These results suggest that bone marrow stromal cells might represent a major source for the cytokine-regulated local production of IL-6 and IL-8 inside human bone marrow.
 ...
PMID:IL-6 and IL-8 production by human bone marrow stromal cells. 951 98

1. Intradermal (i.d.) injection of cytokines, IL-1beta and TNFalpha (5 ng, 60 and 30 min prior) produces a rapid onset up-regulation of des-Arg9-BK-mediated rat paw oedema. Here we analyse the mechanisms involved in des-Arg9-BK-induced oedema in animals pre-treated with IL-1beta or TNFalpha. 2. Co-injection of anti-IL-1beta, anti-TNFalpha and anti-IL-8 (50 ng) significantly inhibited des-Arg9-BK-induced oedema in animals pre-treated with IL-1beta (65, 37 and 42%) or TNFalpha (39, 64, 25%). IL-1 receptor antagonist (IRA, 100 microg) or IL-10 (10 ng) inhibited the oedema caused by des-Arg9-BK, in rats that had received either IL-1beta (67 and 63%) or TNFalpha (46 and 35%). 3. Co-injection of the PKC inhibitors, staurosporine (10 nmol) or RO 318220 (30 nmol) inhibited des-Arg9-BK-induced paw oedema (44 and 42% for IL-1beta and, 53 and 30% for TNFalpha, respectively). Genistein (tyrosine kinase inhibitor, 2.5 mg kg-1, s.c.) or PD 098059 (MAP-kinase inhibitor, 30 nmol) produced marked inhibition of des-Arg9-BK-induced oedema (58 and 39% for IL-1beta and 31 and 35% for TNFalpha respectively). 4. The NF-kappaB inhibitors TLCK (2 mg kg-1, i.p.) and PDCT (100 mg kg-1, i.p.) significantly inhibited the oedema of des-Arg9-BK in IL-1beta (27 and 83%) or TNFalpha (28 and 80%) pre-treated animals. 5. It is concluded that up-regulation of B1 receptors modulated by IL-1beta or TNFalpha involves the release of other cytokines, activation of PKC and tyrosine kinase pathways, co-ordinated with the activation of MAP-kinase and nuclear factor kappaB, reinforcing the view that B1 receptors may exert a pivotal role in modulating chronic inflammatory processes.
 ...
PMID:In vivo B1 kinin-receptor upregulation. Evidence for involvement of protein kinases and nuclear factor kappaB pathways. 1048 16

It has been reported that cigarette smoking worsens alcohol-induced gastric lesions through neutrophil infiltration. We hypothesize that IL-8, a potent chemotactic factor for neutrophil is likely to be involved in this ulcerogenic process. To evaluate this phenomenon, the ability of cigarette smoke extract (CSE) to induce endothelial cell expression of IL-8 was examined. Two different fractions (ethanol or chloroform soluble extracts) of CSE with their chemical types identified showed a time- and dose-dependent increase on IL-8 secretion from ECV304 cell line. Protein kinase C (PKC) inhibitor GF109203X had no effect on IL-8 response in basal secretion and also to these stimuli. Protein tyrosine kinase (PTK) inhibitor genistein and protein kinase A (PKA) inhibitor H8 at respective concentrations significantly reduced chloroform and ethanol soluble extract-induced IL-8 expression by about 34 and 35% respectively at 8 h after incubation. It is concluded that CSE increases IL-8 release from human endothelial cells through PTK and PKA activation.
 ...
PMID:Increased interleukin-8 expression by cigarette smoke extract in endothelial cells. 1113 64

Using human endothelial cells, we define a mechanism that accounts for the induction of interleukin 8 (IL-8) by protein I/IIf, an adhesin from Streptococcus mutans serotype f. We report that protein I/IIf interactions with endothelial cells increased the tyrosine phosphorylation of three cellular components with relative mass of 145,000, 125,000 and 70,000 in endothelial cells. These proteins were identified as phospholipase Cgamma (PLCy), focal adhesion kinase (FAK) and paxillin after immunoprecipitation with monoclonal antibodies (mAbs) and immunoblotting with antiphosphotyrosine mAbs. These results suggested that beta1 integrins could be one of the components implicated in the modulin activity of protein I/IIf. By incubating protein I/IIf with either purified alpha5beta1 integrins or with alpha5beta1 integrins overexpressing CHO cells, we demonstrated that alpha5beta1 integrins act as cell receptors for protein I/IIf. We also showed that protein I/IIf interactions with alpha5beta1 integrins lead to IL-8 secretion. Using specific inhibitors, we demonstrated that protein I/IIf-induced IL-8 release involves mitogen-activated protein kinases (MAPKs), and that PLCgamma and PKC also seem to contribute to protein I/IIf stimulation. However, PI-3K activation is not involved in IL-8 release. Altogether, these results indicate that, after binding to alpha5beta1 integrins, protein I/IIf induces IL-8 release by activating the MAPKs signalling pathways.
 ...
PMID:Involvement of alpha5beta1 integrins in interleukin 8 production induced by oral viridans streptococcal protein I/IIf in cultured endothelial cells. 1120 49

1. Recent data indicate that interleukin (IL)-17 may contribute to neutrophilic airway inflammation by inducing the release of neutrophil-mobilizing cytokines from airway cells. The aim of this study was to evaluate the role of mitogen activated protein kinases in IL-17 induced release of IL-8 and IL-6 in bronchial epithelial cells. 2. Transformed human bronchial epithelial cells (16HBE) were stimulated with either IL-17 or vehicle. Both groups were treated either with SB202190 (inhibitor of p38 MAP kinase), PD98059 (inhibitor of extracellular-signal-regulated kinase [ERK] pathway), Ro-31-7549 (protein kinase C [PKC] inhibitor), LY 294002 (a phosphatidylinositol 3-kinase [PI 3-kinase] inhibitor) or vehicle. IL-6 and IL-8 levels were measured in conditioned media by ELISA. 3. The IL-17-induced release of IL-6 and IL-8 was concentration-dependently inhibited by SB202190 and by PD98059 in bronchial epithelial cells without affecting cell proliferation or survival. 4. Ro-31-7549 and LY294002 had no significant effect on IL-17-induced IL-6 or IL-8 release in bronchial epithelial cells. 4. Taken together, these data indicate a role for p38 and ERK kinase pathways in IL-17-induced release of neutrophil-mobilizing cytokines in human bronchial epithelial cells. These mechanisms constitute potential pharmacotherapeutical targets for inhibition of the IL-17-mediated airway neutrophilia.
 ...
PMID:IL-17-induced cytokine release in human bronchial epithelial cells in vitro: role of mitogen-activated protein (MAP) kinases. 1132 11


1 2 3 4 5 6 7 8 9 Next >>