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)

The present study was designed to investigate the capacity of human mononuclear phagocytes to produce a cytokine chemotactic for monocytes (monocyte chemotactic protein (MCP), alternative acronyms JE, monocyte chemotactic and activating factor, MCP-1, and tumor-derived chemotactic factor). Human PBMC exposed in vitro to bacterial LPS expressed high levels of MCP transcripts. Monocyte-depleted lymphoid cells were not induced to express MCP by LPS. Percoll-gradient purified monocytes were able to express high levels of MCP transcripts. In an effort to exclude a role of contaminating non-monocytic cells, mononuclear phagocytes were separated by flow cytometry and sorting: CD14+ cells exposed to LPS showed high levels of MCP mRNA. LPS-stimulated monocytes released chemotactic activity for monocytes that could be inhibited by absorption with anti-MCP antibodies. IL-1, TNF, IFN-gamma, granulocyte-macrophage-CSF and, to a lesser extent, macrophage-CSF, as well as inactivated streptococci, also induced MCP gene expression. Actinomycin D experiments indicated that induction of MCP in monocytes was gene transcription-dependent. The protein synthesis inhibitor cycloheximide (Cy) blocked IL-1-, TNF-, or LPS-induced MCP gene expression in monocytes. In contrast, expression of the structurally related chemotactic cytokine IL-8 was superinduced by Cy. Moreover, Cy superinduced MCP gene expression in cells other than monocytes, including endothelial cells, smooth muscle cell and fibrosarcoma cells, indicating different mechanisms of regulation in mononuclear phagocytes vs cells of other lineages. The capacity of cells of the monocyte-macrophage lineage to produce a cytokine that recruits and activates circulating monocytes may be of considerable importance in inflammatory and immunologic reactions. Thus, the mononuclear phagocyte system can autonomously regulate the extravasation and activation of immature elements of the same lineage, a key event in inflammation and immunity.
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PMID:Expression of a monocyte chemotactic cytokine by human mononuclear phagocytes. 137 May 16

This investigation was designed to elucidate whether an intracellular version of interleukin 1 receptor antagonist (icIL-1ra) interferes with the action of IL-1 at the level of vascular cells. Recombinant icIL-1ra inhibited the IL-1-induced production of IL-6, IL-8 and monocyte chemotactic protein by human endothelial cells (HEC). Moreover, icIL-1ra inhibited induction of adhesion molecules by IL-1. Endotoxin lipopolysaccharide (LPS), an IL-1 inducer, stimulated a spectrum of functions in EC similar to that activated by IL-1, but icIL-1ra did not interfere with the LPS activation of EC. This observation suggests that induction of extracellular IL-1 is not an important intermediate event in the response of EC to LPS. Unlike LPS-stimulated monocytes, EC exposed to different inducers did not express appreciable levels of IL-1ra mRNA transcripts as assessed by northern blot analysis. IL-1ra produced by mononuclear phagocytes, represents a negative regulator circuit of the action of IL-1 on EC and could be important in the control of vascular participation in inflammation and immunity.
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PMID:Inhibitory effect of recombinant intracellular interleukin 1 receptor antagonist on endothelial cell activation. 137 16

Cytokine-stimulated human osteosarcoma cells (MG-63) secrete several related chemotactic factors, including the neutrophil-activating protein interleukin 8 (IL-8) and the monocyte chemotactic protein (MCP)-1. We describe the isolation and characterization of two novel monocyte chemotactic factors from this tumor cell line. Although these proteins copurified with MCP-1 and IL-8 on heparin-Sepharose, they could be separated by cation-exchange fast protein liquid chromatography and reverse-phase high-performance liquid chromatography. The corresponding 7.5- and 11-kD proteins were NH2-terminally blocked but were identified by sequencing peptide fragments. They showed a primary structure mostly related to that of MCP-1 and were therefore designated MCP-2 and MCP-3, respectively. These molecules can be classified in a subfamily of proinflammatory proteins characterized by the conservation of cysteine residues. MCP-2 and MCP-3 are also functionally related to MCP-1 because they specifically attract monocytes, but not neutrophils, in vitro. The chemotactic potency (specific activity) was comparable for all three MCPs. Intradermal injection of these proteins in rabbits resulted in selective monocyte recruitment in vivo. Since tumor cells are good producers of leukocyte chemotactic factors, it could be questioned whether these molecules can indirectly control tumor growth by attracting leukocytes or whether they rather promote invasion by the secretion of proteases from the attracted cells.
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PMID:Structural and functional identification of two human, tumor-derived monocyte chemotactic proteins (MCP-2 and MCP-3) belonging to the chemokine family. 161 66

The evolution of acute inflammation from initiation through resolution is associated with the changing character of the infiltrating leukocytes. Recruitment of these leukocytes is dependent upon the generation of chemotactic factors that have either global or specific activity for a particular leukocyte. In this manuscript we present data demonstrating that human neutrophils can express mRNA for neutrophil chemotactic factor/interleukin 8 (IL-8), but fail to express mRNA for monocyte chemotactic protein (MCP-1). The expression of IL-8 was observed upon adherence or in response to stimulation with lipopolysaccharide. Maximal IL-8 antigenic production was noted at 24 hrs. These studies demonstrate a disparate expression of chemotactic cytokines by neutrophils.
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PMID:Human neutrophils exhibit disparate chemotactic factor gene expression. 170 91

Supernatants obtained from four HTLV-I transformed cell lines (MT2, MT4, C91/PL, and 81-66/45) induced in vitro migration of monocytes, polymorphonuclear leukocytes (PMN), and lymphocytes. The MT2, C91/PL, and 81-66/45 cell lines expressed both lymphotoxin (LT) and tumor necrosis factor (TNF-alpha) mRNA transcripts, and had TNF biological activity. In contrast, the MT4 cells did not express LT mRNA, had low levels of TNF-alpha transcript, and no TNF activity in the supernatant. Anti-TNF-alpha MAb, which blocks the chemotactic activity of recombinant TNF-alpha, had no inhibitory effect on the induction of migration by the MT2 and MT4 supernatants. Hence, no correlation was evident between TNF and chemotactic activity in supernatants of different HTLV-I-infected cell lines. Upon fractionation on Sephadex G50, the monocyte chemoattractant(s) eluted with two peaks in the 8-12 kD region, a size compatible with the chemotactic cytokines IL-8 and monocyte chemotactic protein (MCP). However, anti-IL-8 and anti-MCP antibodies did not have any effect, and Northern blot analysis showed that HTLV-I-transformed cell lines did not express mRNA transcripts of either IL-8 and MCP. These results demonstrate that HTLV-I transformed T-cell lines produce chemoattractant(s) active on PMN and monocytes, distinct from LT, TNF-alpha, IL-8, and MCP. Production of chemoattractants may play a role in the pathogenesis of diseases associated with HTLV-I infection.
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PMID:Chemoattractant(s) in culture supernatants of HTLV-I-Infected T-cell lines. 172 88

The present study was designed to investigate the effect of membrane proteoglycans (MPG) from Klebsiella pneumoniae on production of the chemotactic cytokine, IL-8, and monocyte chemotactic protein (MCP) by human peripheral blood monocytes. Exposure of human peripheral blood monocytes to MPG in vitro induced high levels of mRNA transcripts for IL-8 and MCP, as assessed by Northern blot analysis. Cytokine gene expression was associated with the production of chemotactic activity in the supernatants. The levels of IL-8 and MCP expression induced by MPG were comparable with those elicited by LPS. Induction of chemotactic cytokines in mononuclear phagocytes may play a role in the immunomodulatory activity of MPG.
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PMID:Chemotactic cytokine gene expression and production induced in human monocytes by membrane proteoglycans from Klebsiella pneumoniae. 175 2

The present study was designed to investigate the capacity of human vascular smooth muscle cells (SMCs) to produce a cytokine chemotactic for monocytes (monocyte chemotactic protein [MCP]) and by way of comparison, a related polypeptide activator of neutrophils (known as interleukin-8 [IL-8] or neutrophil activating protein-1 [NAP-1]. On exposure to IL-1, SMCs released high levels of chemotactic activity for monocytes, which could be removed by absorption with anti-MCP antibodies. MCP production by activated SMCs was comparable to that of IL-1-stimulated umbilical vein endothelial cells. Activated SMCs released appreciable levels of IL-8, as determined by a specific enzyme-linked immunosorbent assay, but little chemotactic activity for neutrophils. IL-1-treated SMCs expressed high levels of both MCP and IL-8 mRNA transcripts, as assessed by Northern blot analysis. Tumor necrosis factor and bacterial lipopolysaccharide but not IL-6 also induced MCP and IL-8 gene expression in SMCs. Nuclear runoff analysis revealed that IL-1 augmented transcription of the MCP and IL-8 genes. The capacity of SMCs to produce a cytokine (MCP) that recruits and activates circulating mononuclear phagocytes may be of considerable importance in the pathogenesis of vascular diseases (e.g., vasculitis and atherosclerosis) that are characterized by monocyte infiltration of the vessel wall.
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PMID:Expression of monocyte chemotactic protein and interleukin-8 by cytokine-activated human vascular smooth muscle cells. 191 3

We report here that human synovial cells stimulated by interleukin-1 alpha and interleukin-1 beta express mRNA for both IL-8 (neutrophil chemotactic peptide) and monocyte chemotactic protein. IL-1 stimulated synovial cells from both osteoarthritis and rheumatoid arthritis patients exhibited similar mRNA expression of interleukin-8 and monocyte chemotactic protein. A capacity to produce factors selectively chemotactic for neutrophils, lymphocytes and monocytes provides a mechanism whereby synovial cells can facilitate inflammatory arthritis.
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PMID:Interleukin-1 induced gene expression of neutrophil activating protein (interleukin-8) and monocyte chemotactic peptide in human synovial cells. 199 47

Inflammation involving the retina and choroid is a common clinical problem, but the mechanisms that elicit and maintain ocular inflammation remain poorly understood. Interposed between the sensory retina and the systemic blood circulation within the choroid is the neural-derived retinal pigment epithelium (RPE), which forms part of the blood-retina barrier. The RPE is actively phagocytic and shares several features with mononuclear phagocytes of bone marrow origin, including the production of a neutrophil chemotactic factor, interleukin 8, after stimulation with interleukin 1 beta (IL-1 beta) or tumor necrosis factor alpha (TNF-alpha). Because monocyte-derived macrophages are present in retinal lesions of many common and blinding diseases, we monitored human RPE cells or monocyte chemotactic protein (MCP) mRNA expression and activity following cytokine stimulation. Cultured human RPE cells were left unstimulated or exposed to recombinant human IL-1 beta, TNF-alpha, or lipopolysaccharide. MCP mRNA expression in RPE cells and biologically active MCP in RPE cell supernatants were present 1 hour after stimulation and maintained for 24 hours. Conditioned media from RPE cells stimulated with 20 ng/ml of IL-1 beta or TNF-alpha for 24 hours contained biologically active monocyte chemotactic activity that rose rapidly from baseline levels over 4 hours and plateaued over the subsequent 20 hours. RPE chemotactic activity was dose dependent using concentrations of these cytokines ranging from 20 pg/ml to 20 ng/ml of 4-hour assays. Time- and concentration-dependent expression of RPE cell MCP mRNA was also found in the same cultures. Peak MCP mRNA expression occurred after 8 hours of stimulation with IL-1 beta or TNF-alpha. Maximal steady-state MCP mRNA expression occurred at 20 ng/ml for IL-1 beta. Immunohistochemical staining using specific anti-MCP antibodies resulted in distinctive RPE cell staining, confirming the presence of MCP in human RPE cells. These findings demonstrate that cytokine-stimulated RPE cells may evoke or augment mononuclear phagocyte-mediated ocular inflammation by synthesizing MCP.
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PMID:Monocyte chemotactic protein gene expression by cytokine-treated human retinal pigment epithelial cells. 204 33

Human articular chondrocytes, when stimulated with interleukin 1 beta (IL 1 beta), tumor necrosis factor-alpha (TNF-alpha), or with the double stranded RNA poly (rI).poly (rC), produce a chemotactic activity for granulocytes. The induction with IL 1 beta could be abolished by an antibody to IL 1 beta but not by an antibody to interleukin 6 (IL 6), indicating that the latter is not a mediator for the production of chemotactic activity. The inducers had no direct chemotactic effect on granulocytes. The granulocyte chemotactic factor from chondrocytes was characterized with a specific antibody against leukocyte-derived interleukin 8 (IL 8). The specificity of this antibody was demonstrated by immunochemical and biological criteria such that it could immunoprecipitate only the 6-7 kDa IL 8 protein from fibroblasts, and that it did not neutralize a structurally related monocyte chemotactic protein. This antibody against IL 8 completely neutralized the granulocyte chemotactic activity from stimulated chondrocytes. This demonstrates the identity of chondrocyte IL 8 with leukocyte- and fibroblast-derived IL 8. Our data show that leukocyte chemotaxis into the inflamed joint can be mediated by IL 8, induced in both synovial fibroblasts and chondrocytes by the inflammatory cytokines IL 1 and TNF-alpha.
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PMID:Characterization of granulocyte chemotactic activity from human cytokine-stimulated chondrocytes as interleukin 8. 210 16


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