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)

Interleukin (IL) 6, an autocrine growth factor for mesangial cells, and chemokines, which are released from activated mesangial cells and induce leukocyte infiltration, play a critical role in the progression of immune system mediated renal diseases. Since the reciprocal relationship between IL-6 and chemokines in renal inflammation has been barely investigated, we have analyzed whether IL-6 (500 ng/ml), alone or in combination with the soluble form of its receptor (sIL-6R, 200 ng/ml), can induce normal human mesangial cells (NHMC) to release alpha and/or beta chemokines: MCP-1 (monocyte chemoattractant protein 1), IL-8, Rantes (regulated on activation, normal T cell expressed and secreted), and MIP-1alpha (macrophage inflammatory protein 1alpha). Whereas IL-6 or sIL-6R alone were ineffective in inducing significant chemokine release from NHMC, the simultaneous treatment with IL-6 and sIL-6R showed a significant interaction, leading to a strong synergic effect on MCP-1 synthesis and release without exerting any relevant activity on IL-8, Rantes, or MIP-1alpha. Consistently with the unresponsiveness to IL-6, mRNA and protein expression analysis of the two subunits which form the functional IL-6 receptor showed that NHMC express only the gp130 signal-transducing chain and not the subunit-specific IL-6R (gp80). These findings support an unexpected role of the IL-6 system in kidney inflammatory reactions through the selective regulation of monocyte recruitment.
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PMID:Selective induction of MCP-1 in human mesangial cells by the IL-6/sIL-6R complex. 1064 81

Interferon-gamma-inducible 10 kd protein (IP-10) is an ELR (Glu-Leu-Arg)(-) alpha chemokine with known chemotactic effects on T cells and monocytes, as well as anti-viral, anti-angiogenic, and anti-tumor effects. Previous studies have demonstrated that in cultured rat astrocytes and microglia, stimulation with LPS or virus can induce the expression of IP-10. In this study, we determined the pattern of IP-10 gene induction in primary human microglia and astrocytes by cytokines and LPS using ribonuclease protection assay. The expression of IP-10 mRNA was compared with that of other alpha (IL-8) and beta chemokines. The results showed that in human microglia, IP-10 expression was induced equally potently by LPS, IFNbeta or IFNgamma. "Proinflammatory" cytokines IL-1beta or TNFalpha also induced small amounts of IP-10 mRNA. "Anti-inflammatory" cytokines IL-4, IL-10 and TGFbeta were ineffective in inducing IP-10 in microglia. In human astrocytes, induction of IP-10 mRNA by cytokines was similar to that in microglia. LPS, however, was ineffective in inducing IP-10 in human astrocytes. The monocyte chemoattractant beta-chemokine I-309 mRNA was induced in human astrocytes and microglia by IFNbeta or IFNgamma, or by LPS in microglia, showing a tight co-regulation with IP-10 mRNA expression. In contrast to the potent induction of IP-10 and I-309 by IFNs in human glia, the ELR(+) alpha chemokine IL-8 mRNA was induced by IL-1beta and TNFalpha, and to a lesser extent by IFNbeta in microglia. IFNbeta but not IFNgamma was effective in inducing the expression of beta chemokines MIP-1alpha and MIP-1beta in human microglia, with the levels of mRNA similar to those induced by IL-1beta or TNFalpha. Neither MIP-1alpha nor MIP-1beta mRNAs were induced by any stimulation in human astrocytes. The induction of RANTES mRNA in microglia by IFNbeta, IL-1beta or TNFalpha was variable, showing no to low level expression depending on the case, whereas LPS provided a consistent inducing signal. In astrocytes, only cytokine combinations (IFN + IL-1beta) effectively induced the RANTES mRNA. These results demonstrate that distinct sets of chemokine genes are induced in human glial cells by cytokines and interferons. These results may have wide implications for inflammatory, vascular and neoplastic diseases of the CNS.
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PMID:Distinct patterns of stimulus-inducible chemokine mRNA accumulation in human fetal astrocytes and microglia. 1069 46

Tissue distribution of dendritic cells was investigated in eight cases of papillary carcinoma of the thyroid using immunohistochemistry. Most dendritic cells had an immature phenotype (CD1a++, CD11c+, CD40+, CD86-, HLA-DR-) and were located at the invasion edge of the tumor. This pattern of distribution was profoundly different from that of CD68+ macrophages, which were evenly distributed throughout the tumor. The ability of tumor cells to release chemotactic factors active on dendritic cells was investigated in primary cultures of the same cases of papillary carcinoma, and was compared to that of the corresponding normal thyroid cells obtained from the tumor-free contralateral lobe. Chemotactic activity of culture supernatants was tested against dendritic cells in a chemotaxis chamber. It was found that papillary carcinoma cells were active in releasing chemotactic activity, that hepatocyte growth factor (HGF; 100 ng/ml) or interleukin (IL)-1beta (10(3) U/ml) induced a fourfold increase in the amount of chemotactic activity released, and that normal thyroid cells obtained from the same patients were as effective as tumor cells. Characterization of chemokines at RNA level revealed that unstimulated cells contain large amounts of IL-8 and monocyte chemotactic protein (MCP)-1 RNAs, and that stimulation with HGF or IL-1beta induced RNAs for regulated upon activation normal T expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-3alpha, interferon-gamma-inducible protein 10 (IP-10), and, to a lesser extent, MIP-1alpha and MIP-1beta. The possibility that HGF/Met interaction has a biological role in vivo was investigated in serial sections of six tumors immunostained for CD1a+, Met protein, and HGF. It was found that all six tumors were intensely and diffusely positive for Met protein, that HGF staining was present in tumor cells of the advancing edge, and that HGF+/Met+ tumor cell nests were infiltrated by CD1a+ dendritic cells. The foregoing observations are consistent with the possibility that HGF stimulation of Met+ tumor cells is one of the molecular mechanisms involved in the recruitment of dendritic cells.
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PMID:Papillary carcinoma of the thyroid: hepatocyte growth factor (HGF) stimulates tumor cells to release chemokines active in recruiting dendritic cells. 1070 99

We have previously demonstrated that a tartrate-resistant acid phosphatase (TRAP)-positive subpopulation of mononuclear cells isolated from collagenase digests of human osteoclastoma tissue exhibits an osteoclast phenotype and can be induced to resorb bone. Using these osteoclast precursors as a model system, we have assessed the chemotactic potential of 16 chemokines. Three CC chemokines, the recently described CKbeta-8, RANTES, and MIP-1alpha elicited significant chemotactic responses. In contrast, 10 other CC chemokines (MIP-1beta, MCP-1, MCP-2, MCP-3, MCP-4, HCC-1, eotaxin-2, PARC, SLC, ELC) and 3 CXC chemokines (IL-8, GROalpha, SDF-1) were inactive. None of these chemokines showed any chemotactic activity for either primary osteoblasts derived from human bone explants or the osteoblastic MG-63 cell line. The identity of the osteoclast receptor that mediates the chemotactic response remains to be established. However, all three active chemokines have been reported to bind to CCR1 and cross-desensitization studies demonstrate that RANTES and MIP-1alpha can partially inhibit the chemotactic response elicited by CKbeta-8. CKbeta-8, the most potent of the active CC chemokines (EC(max) 0.1-0.3 nM), was further characterized with regard to expression in human bone and cartilage. Although expression is not restricted to these tissues, CKbeta-8 mRNA was shown to be highly expressed in osteoblasts and chondrocytes in human fetal bone by in situ hybridization. In addition, CKbeta-8 protein was shown to be present in human osteophytic tissue by immunolocalization. These observations suggest that CKbeta-8, and perhaps other chemokines, may play a role in the recruitment of osteoclast precursors to sites of bone resorption.
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PMID:CKbeta-8 [CCL23], a novel CC chemokine, is chemotactic for human osteoclast precursors and is expressed in bone tissues. 1073 95

Nucleic acid immunization has been shown to induce both antigen-specific cellular and humoral immune responses in vivo. Moreover, immune responses induced by DNA immunization can be enhanced by the use of molecular adjuvants. For example, coadministration of costimulatory molecules (CD80 and CD86), proinflammatory cytokines (interleukin-1alpha [IL-1alpha], tumor necrosis factor-alpha [TNF-alpha, and TNF-beta), Th1 cytokines (interleukin-2 [IL-2], IL-12, IL-15, and IL-18), Th2 cytokines (IL-4, IL-5, and IL-10), and granulocytes-macrophage colony-stimulating factor (GM-CSF) with DNA vaccine constructs leads to modulation of the magnitude and direction (humoral or cellular) of the immune responses. To further engineer the immune response in vivo, we compared the induction and regulation of immune responses from the codelivery of chemokine (IL-8, interferon-gamma-inducible protein-10 [gammaIP-10], macrophage inhibitory protein-1alpha [MIP-1alpha], and RANTES) genes with codelivery of cytokine genes. We found that as in cytokine gene codelivery, coimmunization with chemokine genes along with DNA immunogen constructs can modulate the direction and magnitude of induced immune responses. We observed that coimmunization with IL-8, gammaIP-10, and MIP-1alpha genes increased the antibody response. We also found that coinjection with IL-8, gammaIP-10, and RANTES resulted in a dramatic enhancement of T helper (Th) proliferation response. Furthermore, among all coinjection combinations, we found that RANTES coinjection caused a high level of cytotoxic lymphocyte (CTL) enhancement. This enhancement of CTL responses observed from the coinjection with RANTES was CD8+ T cell dependent. Together with earlier reports on the utility of coimmunizing immunologically important molecules with DNA immunogens, we demonstrate the potential of this strategy as an important tool for the development of more rationally designed vaccines.
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PMID:Chemokine gene adjuvants can modulate immune responses induced by DNA vaccines. 1084 Oct 77

Several chronic inflammatory changes undergone during chronic haemodialysis are associated with increased pro-inflammatory cytokine production. Although generation of anaphylatoxins has been incriminated in the untoward effects of haemodialysis, it is still debated whether anaphylatoxins stimulate monocyte secretion of TNF-alpha and IL-1. We demonstrate that peripheral mononuclear cells isolated from healthy controls and cultured with complement-activated autologous serum or recombinant C5a induced high levels of IL-1, IL-1ra, IL-8 and MCP-1, low levels of TNFalpha and sTNFRII but no IL-10 and MIP-1alpha. Cytokine production by leukocytes was investigated by FACS analysis in six patients dialysed consecutively with three equivalent low permeability membranes known to activate the complement to different degrees: polysulfone (F6HPS), cellulose acetate (CA) and cuprophane (CP). Percentage of leukocytes expressing IL-1, IL-1ra, TNF-alpha and IL-8 is increased in patients dialysed with CP. Moreover, we show for the first time that haemodialysis is associated with the production of cytokines by circulating neutrophils. Predialysis plasma levels of MCP-1 and TNFRII did not increase during the dialysis session at the time when anaphylatoxin generation was highest. Dialysis with membranes that activate the complement to a high extent induce activation of leukocytes which may explain chronic complications associated with dialysing with CP.
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PMID:In vivo intracellular cytokine production by leukocytes during haemodialysis. 1085 69

Pseudomonas aeruginosa infection of cystic fibrosis patients causes lung damage that is substantially orchestrated by cytokines. In this study, multi-gene probe analysis was used to characterize the ability of the P. aeruginosa mitogen, exoenzyme S, to induce proinflammatory and immunoregulatory cytokines and chemokines. Exoenzyme S strongly induced transcription of proinflammatory cytokines and chemokines (tumor necrosis factor alpha, interleukin-1alpha [IL-1alpha], IL-1beta, IL-6, IL-8, MIP-1alpha, MIP-1beta, MCP-1, RANTES, and I-309), modest transcription of immunoregulatory cytokines (IL-10 and IL-12p40), and weak transcription of Th1 cytokines (IL-2 and gamma interferon). The response occurred early and subsided without evolving over time. These data suggest that cells responding to exoenzyme S would rapidly express proinflammatory cytokines and chemokines that may contribute to pulmonary inflammation in cystic fibrosis.
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PMID:Pseudomonas aeruginosa exoenzyme S induces transcriptional expression of proinflammatory cytokines and chemokines. 1089 95

The healing process of skin wounds is regulated by growth factors which stimulate proliferation of resident cells and their synthesis of extra cellular matrixcomponents. Different leukocyte subtypes (neutrophils, macrophages, lymphocytes and mast cells) participate in wound healing not only as immunological effector cells but also as an important source of inflammatory and growth promoting cytokines. Rapid recruitment of leukocytes and their positioning is tightly regulated by a temporally and spatially changing set of chemokines. Whereas expression of IL-8 and GRO (growth related oncogene) direct early neutrophil recruitment, migration of macrophages is stimulated by MCP-1 (monocyte chemoattractant protein-1) and later, lymphocytes are attracted by IP-10 (gamma-interferon inducible protein-10) and Mig (monokine induced by interferon-gamma). Since chemokines as IL-8 and GRO also stimulate angiogenesis and keratinocyte proliferation, they integrate the inflammatory events with the reparative processes and are potential candidates in the search of wound healing agents.
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PMID:[Role of chemokines in human skin wound healing]. 1092 48

We previously reported an increased percentage of CD14+CD16++ monocytes in the peripheral blood of HIV-infected patients but the physiopathological role of this monocyte subset remains unclear. Cells with a CD14+CD16++ phenotype may be obtained in vitro by culturing human peripheral blood monocytes in the presence of GM-CSF, IL-4 and IL-10. In the present study, we compared the phenotypic and functional characteristics of monocytes-derived CD14+CD16++ cells with those of macrophages and dendritic cells. We show that the CD14+CD16++ cells express dendritic cell markers: CD40, CD80, CD86, HLA-DR, CD11b, CD11c, CD18, CD1a, and CD83. Using RNase protection assay, we demonstrate that CD14+CD16++ cell subset expresses a low ratio of IL-1beta/IL-1ra mRNA and expresses IL-6, MIP-1alpha, MIP-1beta, MCP-1, IL-8, RANTES and I-309 transcripts, similar to dendritic cells. CD14+CD16++ cells produce IL-12, MCP-1 and IL-8, as assessed by flow cytometry. Moreover, CD14+CD16++ cells pulsed with different recall antigens induce a potent autologous T cell proliferation. Altogether, these results provide evidence that CD14+CD16++ cells differentiated in vitro from peripheral blood monocytes exhibit dendritic cell characteristics.
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PMID:CD14+CD16++ cells derived in vitro from peripheral blood monocytes exhibit phenotypic and functional dendritic cell-like characteristics. 1094 Aug 76

Secretion of Monocyte Chemotactic Protein-1 (MCP-1) by fibroblasts infected with Toxoplasma gondii was studied in vitro. A significantly higher MCP-1 secretion was observed 24 h after infection by live tachyzoites. Analysis of chemokine mRNA transcripts by RNase protection assay revealed that this MCP-1 secretion seems associated with increased MCP-1 mRNA expression. However, these increased levels of MCP-1 secretion and expression were not obtained after stimulation by heat-killed tachyzoites or parasites pre-treated by a specific inhibitor of phosphatidylcholine-specific phospholipase C (D609). Inhibition of parasite multiplication by pyrimethamine did not modify MCP-1 secretion. Thus, it appeared that the active penetration of T. gondii in cells was of major importance in the induction of MCP-1 secretion. None of the other chemokines studied by RNase protection assay (lymphotactin, RANTES, IP-10, MIP-1alpha, MIP-1beta, IL-8, and I-309) were expressed after infection by live tachyzoites. We also found that MCP-1 secretion induced by live T. gondii is blocked by inhibitors of nuclear factor (NF)-kappaB activation, ALLN and MG132. Such data indicate that NF-kappaB could be involved in T. gondii-induced MCP-1 production. MCP-1 secretion may contribute to the recruitment of monocytes and lymphocytes and thus participate in the control of T. gondii infection and in its pathogenesis.
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PMID:Toxoplasma gondii induces the secretion of monocyte chemotactic protein-1 in human fibroblasts, in vitro. 1094 4


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