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)

Infiltration of leucocyte populations into sites of inflammation is a common feature in renal diseases. Glomerular mesangial cells are potent producers of a variety of chemokines, leading to specific attraction of distinct types of inflammatory leucocytes into the glomerulus, but so far there is limited knowledge about the responsiveness of mesangial cells to chemokines. We investigated the expression of chemokine receptors and the responsiveness of primary human mesangial cells (HMC) to the chemokines which they produce, namely monocyte chemoattractant protein-1 (MCP-1) and interleukin (IL)-8. We found that mRNAs of the chemokine receptors CCR1, which has been shown before, CCR2 and CXCR2 were induced by T-helper cytokine interferon-gamma (IFNgamma). In IFNgamma-stimulated cells, CCR2 and CXCR2 were detectable by flow cytometry. Following treatment with IFNgamma, HMC responded to MCP-1 and IL-8 with an increase of IL-6 mRNA and protein expression, which was in part blocked by pertussis toxin. Moreover, chemokine stimulation of transfected HMC led to an activation of the immunoregulatory transcription factors NFkappaB and AP-1. Additionally, we found that MCP-1 enhanced the expression of its own mRNA in cells activated to express CCR2, suggesting autocrine feedback mechanisms in MCP-1 regulation. Finally, IFNgamma-activated cells migrated towards an MCP-1 gradient in a chemotaxis assay. These results strengthen the assumption that chemokines are not only involved in the recruitment of immune cells to inflamed tissues, but also seem to play a central role in the autocrine regulation of local tissue cells, leading to proceeding inflammation and possibly contributing to healing by mediating cell growth and migration.
 ...
PMID:IFNgamma induces functional chemokine receptor expression in human mesangial cells. 1198 19

fMLP- or TNF-alpha-stimulated neutrophils produced H(2)O(2) when they adhered to fibrinogen-coated surfaces but not when they adhered to collagen I-, collagen IV-, or Matrigel-coated surfaces. In contrast, LTB4- or IL-8-stimulated neutrophils did not produce H(2)O(2) when they adhered to any of these surfaces. fMLP and TNF-alpha were much more potent than LTB4 and IL-8 in stimulating neutrophils to up-regulate and to activate their alpha(M)beta(2) integrins, as measured by the binding of specific monoclonal antibodies. Pretreatment of neutrophils with pertussis toxin completely blocked their production of H(2)O(2) on fibrinogen-coated surfaces in response to fMLP and their migration through Matrigel in response to fMLP, LTB4, and IL-8. These data show that although the fMLP, LTB4, and IL-8 receptors are coupled to pertussis toxin-sensitive Galpha proteins, they signal neutrophils to initiate qualitatively different effector functions. We propose that the qualitative differences in effector functions signaled by different chemoattractants reflect qualitative differences in using G-protein beta and/or gamma subunits or other factors by their cognate receptors.
 ...
PMID:Different G(i)-coupled chemoattractant receptors signal qualitatively different functions in human neutrophils. 1199 4

Lipoxins, endogenous eicosanoids biosynthetized in vivo at inflammation sites, are potential antiinflammatory mediators. Subjects with severe asthma present chronic inflammation of the airways despite long-term treatment with oral glucocorticoids. Therefore it is of interest to investigate the potential antiinflammatory effects of lipoxin A4 (LXA4) and lipoxin B4 (LXB4) that could attenuate chronic inflammation. In a first time, we detected interleukin (IL)-8 and LXA4 in supernatants of induced sputum. IL-8 was heightened in severe asthma (p = 0.001), whereas high concentrations of lipoxin A4 were present in mild asthma (p = 0.001). We then studied the effects of LXA4 on IL-8 released in vitro. Nanomolar concentrations of LXA4 and LXB4 inhibited the IL-8 released by peripheral blood mononuclear cells from the two groups of patients with asthma: a maximal inhibition of 29.4% (p < 0.01) was observed for patients with mild asthma, and 41.5% inhibition (p < 0.001) for patients with severe asthma at 1 nM and 100 nM LXA4 concentrations, respectively. Polymerase chain reaction analysis indicated that peripheral blood mononuclear cells from patients with asthma expressed the LXA4 receptor mRNA. Moreover, pertussis toxin reversed LXA4- and LXB4-inhibited IL-8 release. These findings suggest that lipoxins have potential antiinflammatory action in asthma.
 ...
PMID:Lipoxins are potential endogenous antiinflammatory mediators in asthma. 1204 28

Chronic airway inflammation is a hallmark of cystic fibrosis (CF). Biological products with chemotactic activity are essential for neutrophil recruitment to sites of inflammation. The presence of a factor with chemotactic activity higher than that of interleukin (IL)-8 in the bronchial secretions of patients with CF has recently been reported. This article reports that the chemotactic activity of this factor remained unaffected by a variety of physical treatments and could be distinguished from those of IL-8, formylmethionylleucylphenylalanine, leukotreine B4, and platelet-activating factor. The factor induced chemotaxis and chemokinesis locomotion of neutrophils, and its chemotactic activity was sensitive to pertussis toxin and thapsigargin. Semipurified preparation of the chemotactic factor increased transiently intracellular Ca(2+) concentration but failed to stimulate the release of neutrophil primary granules and the production of superoxide, suggesting that the semipurified chemotactic factor is a Ca(2+)-dependent chemoattractant of neutrophils, acting via pertussin toxin-sensitive G protein-coupled surface receptors, that directs neutrophil movement toward the airway epithelium.
 ...
PMID:Characterization of a novel chemotactic factor for neutrophils in the bronchial secretions of patients with cystic fibrosis. 1219 11

We provide evidence that platelet factor 4 (PF4), but not the related chemokine neutrophil-activating polypeptide-2, induced highly purified human natural killer (NK) cells to produce interleukin (IL)-8 in a time- and dosage-dependent manner. This ability was retained even while PF4 was bound to heparin. PF4 increased the steady state level of IL-8 mRNA, likely implying a transcriptional effect of PF4. Stimulation of NK cells through the Fc receptor for immunoglobulin G-IIIA was found to synergistically increase the effect of PF4 on IL-8 production but did not affect IL-2-related activities such as cytotoxic activity and proliferation. Pertussis toxin did not block the PF4-derived IL-8 production in NK cells, but this response was sensitive to wortmannin, implicating a role of phosphatidylinositol 3-kinase in the intracellular signaling pathway triggered by PF4. Our results characterize a new capacity for PF4 and provide further evidence for the pivotal role of NK cells in the environment of inflammation.
 ...
PMID:Platelet factor 4 induces human natural killer cells to synthesize and release interleukin-8. 1222 28

In lymphoid tissues coinfected with Mycobacterium avium complex (MAC) and HIV-1, increased viral replication has been observed. This study investigates the role of MAC in perpetuating both infections through the recruitment of monocytes as potential new hosts for bacteria and HIV-1. Increased numbers of macrophages were present in the lymph nodes of patients with dual infection as compared with lymph nodes from HIV(+) patients with no known opportunistic pathogens. In a coculture system, monocyte-derived macrophages were treated with HIV-1 or M. avium and its constituents to further define the mechanism whereby MAC infection of macrophages initiates monocyte migration. Monocyte-derived macrophages treated with bacteria or bacterial products, but not HIV-1, induced a rapid 2- to 3-fold increase in recruitment of monocytes. Pretreatment of the monocytes with pertussis toxin inhibited the migration of these cells, indicating a G protein-linked pathway is necessary for induction of chemotaxis and thus suggesting the involvement of chemokines. Analysis of chemokine mRNA and protein levels from M. avium-treated cultures revealed MAC-induced increases in the expression of IL-8, macrophage-inflammatory protein (MIP)-1alpha, and MIP-1beta with donor-dependent changes in monocyte chemotactic protein-1. Pyrrolidine dithiocarbamate, an antioxidant, inhibited the activation of NF-kappaB and significantly diminished the MAC-induced chemotaxis, concurrently lowering the levels of monocyte chemotactic protein-1 and MIP-1beta. These data demonstrate that MAC induces macrophage production of multiple chemotactic factors via NF-kappaB to promote monocyte migration to sites of MAC infection. In vivo, opportunistic infection may act as a recruitment mechanism in which newly arrived monocytes serve as naive hosts for both MAC and HIV-1, thus perpetuating both infections.
 ...
PMID:Mycobacterium avium complex promotes recruitment of monocyte hosts for HIV-1 and bacteria. 1224 82

Host response to injury and infection is accompanied by a rapid rise in the blood of acute-phase proteins such as serum amyloid A (SAA). Although SAA has been used as a marker for inflammatory diseases, its role in the modulation of inflammation and immunity has not been defined. Human neutrophils respond to SAA with secretion of the proinflammatory cytokines interleukin 8 (IL-8) and, to a lesser extent, tumor necrosis factor alpha (TNF-alpha). The induction of IL-8 secretion by SAA involves both transcription and translation and correlates with activation of nuclear factor kappaB (NF-kappaB). The proximal signaling events induced by SAA include mobilization of intracellular Ca(2+) and activation of the mitogen-activated protein kinases ERK1/2 and p38, both required for the induced IL-8 secretion. Pertussis toxin effectively blocks SAA-induced IL-8 secretion indicating involvement of a Gi-coupled receptor. Overexpression of FPRL1/LXA4R in HeLa cells results in a significant increase of the expression of NF-kappaB and IL-8 luciferase reporters by SAA, and an antibody against the N-terminal domain of FPRL1/LXA4R inhibits IL-8 secretion. Lipoxin A4, which binds to FPRL1/LXA4R specifically, decreases SAA-induced IL-8 secretion significantly. Collectively, these results indicate that the cytokine-like property of SAA is manifested through activation of the Gi-coupled FPRL1/LXA4R, which has been known to mediate the anti-inflammatory effects of lipoxin A4. The ability of FPRL1/LXA4R to mediate 2 drastically different and opposite functions suggests that it plays a role in the modulation of inflammatory and immune responses.
 ...
PMID:Serum amyloid A induces IL-8 secretion through a G protein-coupled receptor, FPRL1/LXA4R. 1239 91

Cell polarization is required for directed cell migration. We investigated the role of the calcium-dependent protease calpain during neutrophil chemotaxis and found that calpain inhibition induced neutrophil adhesion, polarization, and rapid chemokinesis in the absence of exogenous activators. Resting neutrophils display constitutive calpain activity with mu-calpain being the predominant active isoform. Our findings suggest that constitutive calpain activity in resting neutrophils may function as a negative regulator of protrusion and migration. Specific inhibition of mu-calpain, but not m-calpain, induced neutrophil polarization and chemokinesis. In contrast to IL-8-induced chemokinesis, the chemokinesis induced by calpain inhibition was not reduced in the presence of pertussis toxin, suggesting that calpain functions downstream of G protein-coupled receptors. Further, both calpain inhibition and stimulation with IL-8 and formyl-Met-Leu-Phe (fMLP) induced an increase in Cdc42 and Rac activation. These findings are consistent with the involvement of calpain in chemotaxis pathways. Accordingly, calpain inhibition decreased neutrophil chemotaxis and directional persistence in a gradient of IL-8 and fMLP. Together, these data reveal a previously uncharacterized function for calpain in neutrophils and suggest that localized modulation of calpain activity may regulate neutrophil chemotaxis downstream of G-protein-coupled receptors.
 ...
PMID:Calpain regulates neutrophil chemotaxis. 1264 22

1. Extracellular nucleotides are the focus of increasing attention for their role as extracellular mediators since they are released into the extracellular environment in a regulated manner and/or as a consequence of cell damage. 2. Here, we show that human eosinophils stimulated with different nucleotides release eosinophil cationic protein (ECP) and the chemokine interleukin 8 (IL-8), and that release of these two proteins has a different nucleotide requirement. 3. Release of ECP was triggered in a dose-dependent manner by ATP, UTP and UDP, but not by 2'-&3'-o-(4-benzoyl-benzoyl)adenosine 5'-triphosphate (BzATP), ADP and alpha,beta-methylene adenosine 5' triphosphate (alpha,beta-meATP). Release of IL-8 was triggered by UDP, ATP, alpha,beta-meATP and BzATP, but not by UTP or ADP. Pretreatment with pertussis toxin abrogated nucleotide-stimulated ECP but not IL-8 release. 4. Release of IL-8 stimulated by BzATP was fully blocked by the P2X(7) blocker KN-62, while release triggered by ATP was only partially inhibited. IL-8 secretion due to UDP was fully insensitive to KN-62 inhibition. 5. Priming of eosinophils with GM-CSF increased IL-8 secretion irrespectively of the nucleotide used as a stimulant. 6. It is concluded that extracellular nucleotides trigger secretion of ECP by stimulating a receptor of the P2Y subfamily (possibly P2Y(2)), while, on the contrary, nucleotide-stimulated secretion of IL-8 can be due to activation of both P2Y (P2Y(6)) and P2X (P2X(1) and P2X(7)) receptors.
 ...
PMID:Stimulation of P2 purinergic receptors induces the release of eosinophil cationic protein and interleukin-8 from human eosinophils. 1271 24

There is increasing evidence that both cell adhesion molecules and soluble factors are involved in tumor metastasis. We have found that endothelial cells secrete chemoattractants that can induce melanoma cell chemotaxis. Protein separation on an ion-exchange column shows the association of IL-8 with fractions that contain the chemoattractant activity. This activity is completely lost from the conditioned medium after immunoprecipitation with anti-IL-8 antibodies, indicating that IL-8 is the major melanoma chemoattractant secreted by endothelial cells. IL-877, the predominant endothelial IL-8 isoform that contains 77 amino acids, is found to be twice as potent as the more common 72-amino acid isoform IL-872. Antibody inhibition studies indicate that the chemotactic response of melanoma cells is mediated by the CXC-chemokine receptor CXCR1 and not by the more promiscuous CXCR2. When stimulated by tumor necrosis factor alpha, the nonresponsive WM35 melanoma cells synthesize a higher level of CXCR1 and become chemotactic toward interleukin (IL)-8. Pretreatment of cells with pertussis toxin nullifies their chemotactic response, suggesting the involvement of G proteins. Antibodies against either IL-8 or CXCR1 inhibit melanoma transendothelial migration in a coculture assay by 30%. These results are consistent with a role for IL-8-induced chemotaxis in the transendothelial migration of melanoma cells.
 ...
PMID:Interleukin-8 secreted by endothelial cells induces chemotaxis of melanoma cells through the chemokine receptor CXCR1. 1273 12


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>