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 expression and regulation of seven human members of a family of related cytokines, which play a role as effectors of inflammation, were analysed in hemopoietic cells and in fibroblasts. In T lymphocytes all genes: platelet basic protein (PBP); platelet factor 4 (PF-4); IL-8/NAP-1; IP-10; GRO; pAT464 and pAT744 were induced by stimulation with phytohemagglutinin and phorbol 12-myristate 13-acetate (PHA/PMA). In contrast to T cells, only some of the genes were induced upon terminal differentiation of pro-monocytic cells and upon serum stimulation of resting fibroblasts. This distinct expression indicates functional differences of the individual proteins. The expression of inflammatory mediators in fibroblasts suggests the involvement of these cells in inflammatory reactions.
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PMID:Cell type specific expression of members of the IL-8/NAP-1 gene family. 833 26

We examined the genetic expression of 2 CXC chemokines (IL-8, IP-10), 5 CC chemokines (MCP-1, MIP-lalpha, MIP-1beta, RANTES, 1309) and 1 C chemokine (SCM-1/lymphotactin/ATAC) in various human T-cell lines. By Northern blot analysis, HTLV-1-positive T-cell lines were found to express a number of chemokine genes at variable levels and in different combinations. However, none of the chemokine genes was expressed in HTLV-1-negative T-cell lines. We further confirmed secretion of 3 chemokines (IL-8, MIP-1alpha and RANTES) by some HTLV-1-positive T-cell lines. To examine the role of the HTLV-1-encoded transactivator Tax in the induction of these chemokine genes, we used JPX-9 and JPX-M, which were stably transformed with tax and non-functional tax, respectively, under the control of a metallothionein promoter. Induction of tax in JPX-9 with Cd2+ was accompanied by rapid induction of IL-8, IP-10, MIP-1alpha, MIP-1beta, 1309 and SCM-1 as determined by reverse transcription PCR. No such induction was seen in JPX-M. We thus suggest that Tax is, at least in part, responsible for constitutive expression of certain chemokine genes in HTLV-1-infected T cells. Aberrant production of various chemokines by HTLV-1- infected T cells may impact on the pathophysiology of HTLV-1-associated diseases.
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PMID:Constitutive expression of various chemokine genes in human T-cell lines infected with human T-cell leukemia virus type 1: role of the viral transactivator Tax. 860 55

Human peripheral blood leukocytes (hPBL) are a rich source of natural leukocyte interferon (IFN-alpha) when treated with Sendai virus. Sendai virus treatment of hPBL will also result in significant production of several chemokines and cytokines such as macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, RANTES, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-8, in a time-dependent way. A significant amount of MCP-1 is constitutively produced in overnight culture of leukocytes. The most abundant cytokine is IFN-alpha, which is induced to its maximum level approximately 11-15 h after addition of Sendai virus. The amount of IFN-alpha induced at 15 h after Sendai virus treatment is more than 16-fold higher than those of MIP-1alpha, MIP-1beta, and RANTES. IFN-alpha is also induced more than 60-fold higher than TNF-alpha and IL-8. The amount of IL-6 induced is approximately 400-fold less than IFN-alpha. Limited amounts of other cytokines such as IL-1alpha, IL-1beta, macrophage colony-stimulating factor, TNF-beta, and IFN-gamma are also induced in Sendai virus-treated hPBL. No measurable amount of granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, leukemia inhibitory factor, IL-2, IL-3, IL-4, IL-5, IL-7, IL-10, IL-11, or IL-12 was induced in the supernatant of Sendai virus-treated hPBL.
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PMID:Cytokines induced by Sendai virus in human peripheral blood leukocytes. 869 16

A novel family of chemotactic cytokines or chemokines, essential for the directed migration of leukocytes to sites of inflammation, has been identified during the past decade. To obtain microgram amounts of natural chemokines, normal (e.g., freshly isolated leukocytes, connective tissue cell cultures) or malignant cell lines have to be selectively induced with endogenous (cytokines) or exogenous (bacterial, viral, or plant) products. We have developed a four-step procedure that allows for the complete purification of active C-C (MCP-1, MCP-2, MCP-3, RANTES, MIP-1alpha and MIP-1beta) and C-X-C (IL-8, GRO-alpha, GRO-beta, GRO-gamma, GCP-2, ENA-78, IP-10, PF-4, and CTAPIII/betaTG/NAP-2) chemokines from bulk volumes of culture supernatant. This method is applicable for the isolation of recombinant chemokines. Conditioned medium was first concentrated and partially purified on silicic acid or controlled pore glass beads. Further purification to homogeneity was achieved using heparin-Sepharose or antibody affinity chromatography, cation exchange FPLC, and reverse-phase HPLC. Purification of chemokines was monitored by testing column fractions for biological (chemotaxis) or immuno (RIA, ELISA) activity and protein content (SDS-PAGE). Homogeneous proteins were identified by amino-terminal or internal protein sequence analysis.
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PMID:Purification and Identification of Natural Chemokines 881 48

Among leukocytes, only monocytes and macrophages were found to be highly susceptible to an infection by influenza A virus. After infection, de novo viral protein synthesis was initiated but then interrupted after 4-6 h. Most macrophages died by apoptosis within 25-30 h. Before cell death, however, macrophages responded to influenza A virus with a high cytokine gene transcription and subsequent release of tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), IL-6, interferon (IFN)-alpha/beta, and CC-chemokines. The basic mechanisms of virus-induced cytokine expression are still unknown and appear to involve transcription factors such as nuclear factor-kappaB and AP-1 which, however, were only activated for 2 h and declined below control values thereafter. After influenza A virus infection, only the mononuclear cell attracting CC-chemokines macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, and RANTES were produced while the prototype neutrophil CXC-chemoattractants IL-8 and GRO-alpha were entirely suppressed. This selective induction of CC-chemokines may explain the preferential influx of mononuclear leukocytes into virus-infected tissue. Our data show that monocytes and macrophages represent a primary target for an influenza A virus infection. Thus, the mononuclear phagocyte response leads to a rapid proinflammatory reaction and an enhanced immigration of mononuclear leukocytes, which may condition the infected host for the subsequent virus antigen-specific defense.
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PMID:Susceptibility of mononuclear phagocytes to influenza A virus infection and possible role in the antiviral response. 910 26

The beta-chemokines monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein 1 alpha (MIP-1alpha), MIP-1beta and regulated on activation, normal T cells, expressed and secreted (RANTES) induced the in vitro migration of the monocytic cell line MonoMac-6. MCP-1 exhibits the most potent chemotactic effect on this cell line while MIP-1alpha, RANTES and to a lesser extent MIP-1beta were more moderate inducers of cell migration. MonoMac-6 migration in response to chemokines was shown to be a chemotactic and not a chemokinetic response, which was inhibited by pertussis and cholera toxins suggesting a role for G proteins in chemokine receptor-mediated signalling in these cells; chemotaxis of MonoMac-6 cells in response to MCP-1 was abrogated by the addition of anti-MCP-1 antibody. The response of MonoMac-6 cells to the alpha-chemokines IL-8, IP-10, growth-related peptide (Gro) alpha and MIP-2beta was substantially weaker than to the beta-chemokines. MCP-1 caused an alteration in cellular morphology by increasing ruffling at the cell membrane and the number of cells exhibiting extended pseudopodia. The chemotactic response of MonoMac-6 cells to beta-chemokines was compared with less well-differentiated myelomonocytic cell lines. THP-1 showed a similar, but weaker response to the beta-chemokines while both HL60 and U937 failed to respond to any member of this subfamily when tested under the same conditions. These results suggest that the differentiation status of cells of monocytic lineage may affect their response to beta-chemokines.
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PMID:Migration responses of human monocytic cell lines to alpha- and beta-chemokines. 923 15

Dendritic cells (DC) are migratory cells that exhibit complex trafficking properties in vivo. The present study was designed to characterize receptor expression and responsiveness to chemoattractants of human DC obtained from PBMC by culture with granulocyte/macrophage-CSF and IL-13. DC expressed appreciable levels of the CCR1, CCR2, and CCR5 receptors for the CC chemokines and the chemokine receptors CXCR1, CXCR2, and CXCR4. DC increased intracellular free calcium and migrated in response to the CC chemokines MCP-3, MCP-4, RANTES, MIP-1alpha, MIP-1beta, and MIP-5/HCC2 and the CXC chemokine SDF-1. In contrast, the CC chemokines MCP-1 and eotaxin had little or no activity in the concentration range tested (up to 1 microg/ml). IL-8 and Gro-beta (CXC) and lymphotactin (C chemokines) were also inactive. DC did not respond to 5-HETE, whereas platelet-activating factor was an active agonist. Selected chemokines active on DC in terms of migration and calcium fluxes were examined for their capacity to modulate endocytosis and Ag presentation. Under conditions in which TNF-alpha was active, MCP-1, MCP-3, MIP-1alpha, and RANTES did not affect these two responses. Thus, among hemopoietic elements, DC respond to a unique set of CC and CXC chemokines, and their responsiveness is restricted to migration with no effect on Ag capture and presentation. Chemokines may play a role in the trafficking of DC under resting or stimulated conditions. Chemokine receptors expressed in DC are likely to underlie HIV infection of this cell type.
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PMID:Receptor expression and responsiveness of human dendritic cells to a defined set of CC and CXC chemokines. 925 66

A growing family of proteins, known as the chemokines, play an important role in the recruitment and activation of inflammatory cells. The purpose of these studies was to characterize the chemokine receptors present on human sodium butyrate differentiated EoL-3 cells (dEoL-3 cells). Using a combination of 3' rapid amplification of cDNA ends and nested polymerase chain reaction, we detected mRNA for CC chemokine receptor (CCR)1, CCR2, CCR3 and low level of CCR5. Radioligand binding studies demonstrated high-affinity saturable binding for both 125I-macrophage inflammatory protein (MIP)-1alpha and 125I-regulated upon activation normal T cell expressed and secreted (RANTES) with Kd values of 1.4 and 7 nM, respectively. Competition binding with chemokines demonstrated exactly the same rank order of potency for displacement of both ligands: MIP-1alpha approximately monocyte chemoattractant protein (MCP)-3 approximately RANTES > MIP-1beta >> MCP-1 >>> IL-8. RANTES, MCP-3 and MIP-1alpha all produced concentration-dependent transient increases in intracellular calcium concentrations in dEoL-3 cells. Desensitization studies indicated that RANTES, MIP-1alpha and MCP-3 interacted at the same receptor, which is identical in characterization to the cloned CCR1. 125I-MCP-1 also demonstrated high-affinity satuable binding to dEoL-3 cells with a Kd value of 0.4 nM. Competition studies showed that MCP-3 was slightly more potent than MCP-1 and MCP-2. MIP-1alpha, MIP-1beta and RANTES were unable to displace 125I-MCP-1. Addition of either MCP-1 or MCP-3 produced a concentration-dependent elevation of intracellular calcium with a maximun response 2-fold higher than that seen with RANTES or MIP-1alpha. Desensitization studies indicated that MCP-1 and MCP-3 function through CCR2 on these cells. Thus binding and functional studies indicate that dEoL-3 cells express functional CCR1 and CCR2 and that these cells may serve as an important system with which to study the regulation and role of these receptors.
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PMID:Characterization of functional chemokine receptors (CCR1 and CCR2) on EoL-3 cells: a model system to examine the role of chemokines in cell function. 933 50

Induction of chemokine gene expression from peripheral blood mononuclear cells (PBMCs) stimulated by proinflammatory cytokines plays an important role in both wound repair and response to infectious agents. In the present study, we show that the proinflammatory cytokine interleukin-6 (IL-6) potently induced mRNA expression and secretion of the CC chemokine monocyte chemotactic protein 1 (MCP-1) in PBMCs. In addition, because human immunodeficiency virus (HIV) infection in vivo and in vitro has been shown to dysregulate the production of and/or the response to cytokines, PBMCs from both healthy uninfected and HIV-infected individuals were studied for their constitutive and IL-6-induced expression of MCP-1. No substantial differences were observed between the two groups of individuals. In addition, IL-6 upregulated MCP-1 expression in the promonocytic cell line U937 and in its chronically HIV-infected counterpart, U1. In these cell lines, IL-6 selectively induced MCP-1 and not other chemokines, including regulated upon activation normal T cells expressed and secreted (RANTES), macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and IL-8. IL-6 induction of MCP-1 was partially inhibited by hydrocortisone in U1 cells. Thus, IL-6 activates PBMCs to secrete MCP-1, a CC chemokine pivotal for monocyte recruitment in tissue and organs in which important inflammatory events occur.
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PMID:Interleukin-6 induces monocyte chemotactic protein-1 in peripheral blood mononuclear cells and in the U937 cell line. 941 93

The beta-chemokines RANTES, MIP-1alpha, and MIP-1beta have been shown to inhibit the infection of T cells by macrophage-tropic HIV-1 strains by blocking env-driven HIV-1 fusion through competition for the chemokine receptors or receptor downregulation. This study was aimed at testing whether beta-chemokines also inhibit the productive infection of monocyte-derived macrophages (MDMs) by a monocytotropic HIV-1 strain, by using virus yield assays. The action of the beta-chemokines MIP-1alpha, MIP-1beta, and RANTES was captured with that of the alpha-chemokine interleukin 8 (IL-8) and of interferon alpha (IFN-alpha), which is a well-known broad-range inhibitor of viral replication. While IL-8 did not inhibit HIV-1 BaL replication in MDMs, the beta-chemokines were dose-dependently inhibitory. RANTES was the most effective, reaching at 300 ng/ml a protection similar to that obtained with IFN-alpha at 1000 IU/ml, and was even more inhibitory when added to MDMs after virus attachment. In contrast to IFN-alpha, the antiviral activity of beta-chemokines was restricted to HIV, because another virus was not inhibited. As compared with untreated MDMs, full-length proviral DNA at day 1 postinfection was inhibited in MDMs treated with RANTES either before or after the absorption phase, and even more so in IFN-treated MDMs, whereas in IL-8-treated MDMs no inhibition was observed. Our results indicate that in MDMs both RANTES and IFN affect early steps of HIV-1 BaL replication, preceding the completion of viral DNA synthesis.
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PMID:Inhibition of HIV type 1 BaL replication by MIP-1alpha, MIP-1beta, and RANTES in macrophages. 949 13


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