UNIPROT:P10145 - FACTA Search

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Query: UNIPROT:P10145 (IL-8)
23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

The alpha-chemokine receptor CXCR4 has recently been shown to support syncytium formation mediated by strains of feline immunodeficiency virus (FIV) that have been selected for growth in the Crandell feline kidney cell line (CrFK-tropic virus). Given that both human and feline CXCR4 support syncytium formation mediated by FIV, we investigated whether human stromal cell-derived factor (SDF-1) would inhibit infection with FIV. Human SDF-1alpha and SDF-1beta bound with a high affinity (K(D)s of 12.0 and 10.4 nM, respectively) to human cells stably expressing feline CXCR4, and treatment of CrFK cells with human SDF-1alpha resulted in a dose-dependent inhibition of infection by FIV(PET). No inhibitory activity was detected when the interleukin-2 (IL-2)-dependent feline T-cell line Mya-1 was used in place of CrFK cells, suggesting the existence of a CXCR4-independent mechanism of infection. Furthermore, neither the human beta-chemokines RANTES, MIP-1alpha, MIP-1beta, and MCP-1 nor the alpha-chemokine IL-8 had an effect on infection of either CrFK or Mya-1 cells with CrFK-tropic virus. Envelope glycoprotein purified from CrFK-tropic virus competed specifically for binding of SDF-1alpha to feline CXCR4 and CXCR4 expression was reduced in FIV-infected cells, suggesting that the inhibitory activity of SDF-1alpha in CrFK cells may be the result of steric hindrance of the virus-receptor interaction following the interaction between SDF and CXCR4. Prolonged incubation of CrFK cells with SDF-1alpha led to an enhancement rather than an inhibition of infection. Flow cytometric analysis revealed that this effect may be due largely to up-regulation of CXCR4 expression by SDF-1alpha on CrFK cells, an effect mimicked by treatment of the cells with phorbol myristate acetate. The data suggest that infection of feline cells with FIV can be mediated by CXCR4 and that, depending on the assay conditions, infection can be either inhibited or enhanced by SDF-1alpha. Infection with FIV may therefore prove a valuable model in which to study the development of novel therapeutic interventions for the treatment of AIDS.
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PMID:Modulation of feline immunodeficiency virus infection by stromal cell-derived factor. 949 65

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, and the fourth leading cause of death in the United States. Its pathological changes include amyloid beta deposits, neurofibrillary tangles and a variety of 'inflammatory' phenomenon such as activation of microglia and astrocytes. The pathological significance of inflammatory responses elicited by resident central nervous system (CNS) cells has drawn considerable attention in recent years. Chemokines belongs to a rapidly expanding family of cytokines, the primary function of which is control of the correct positioning of cells in tissues and recruitment of leukocytes to the site of inflammation. Study of this very important class of inflammatory cytokines may greatly help our understanding of inflammation in the progress of AD, as well as other neurodegenerative diseases. So far, immunoreactivity for a number of chemokines (including IL-8, IP-10, MIP-1beta, MIPalpha and MCP-1) and chemokine receptors (including CXCR2, CXCR3, CXCR4, CCR3, CCR5 and Duffy antigen) have been demonstrated in resident cells of the CNS, and upregulation of some of the chemokines and receptors are found associated with AD pathological changes. In this review, we summarize findings regarding the expression of chemokines and their receptors by CNS cells under physiological and pathological conditions. Although little is known about the potential pathophysiological roles of chemokines in CNS, we have put forward hypotheses on how chemokines may be involved in AD.
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PMID:Chemokines/chemokine receptors in the central nervous system and Alzheimer's disease. 1019 Jun 88

Differential cDNA displays between hepatocellular carcinoma and adjacent non-malignant tissues have previously detected a PCR product, hIRH (human intercrine reduced in hepatomas), equivalent to SDF1alpha/PBSF whose mRNA was lost from human hepatocellular carcinoma and other malignant and pre-malignant samples and malignant cell lines. There are no reports to date of the mRNA status of the receptor for hIRH/SDF1alpha/PBSF, CXCR4 in malignant tissues. We report here that there is a reduction in the mRNA expression of CXCR4 in hepatocellular carcinoma as estimated by Northern blot and RT-PCR and compared to the adjacent non-malignant tissue. The average (mean SD) tumor/normal ratio for CXCR4 mRNA expression, determined by RT-PCR, was 0.65 0.36 in 10 pairs of hepatocellular carcinomas. There was no consistent loss of CXCR4 mRNA expression in a range of malignant cell lines. The 3'-non-coding region of hIRH, had typical early response gene element sequences. Despite the presence of these 3'-elements there was no induction of hIRH gene expression in human lung carcinoma A549 cells by tumor necrosis factor alpha, interleukin-2, lipopolysaccharide or phorbol myristic acetate, nor in human melanoma cell line SB-2 by uv irradiation, under conditions which induced the homologue CXC intercrine IL-8 expression. Furthermore, there was no induction of hIRH gene expression, but rather a suppression, upon serum or cytokine addition to serum-deprived fibroblast cell lines, to an in vitro mouse bone marrow preparation, and to monocytic cell line THP-1.
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PMID:Reduced expression of the CXCR4 receptor mRNA in hepatocellular carcinoma and lack of inducibility of its ligand alpha-chemokine hIRH/SDF1alpha/PBSF in vitro. 1020 Mar 43

When naive T lymphocytes are activated and differentiate into memory/effector cells, they down-regulate receptors for constitutive chemokines such as CXCR4 and CCR7 and acquire receptors for inflammatory chemokines such as CCR3, CCR5 and CXCR3, depending on the Th1/Th2 polarization. This switch in chemokine receptor usage leads to the acquisition of the capacity to migrate into inflamed tissues. Using RNase protection assays, staining with specific antibodies, and response to recombinant chemokines, we now show that following TCR stimulation, memory/effector T cells undergo a further and transient switch in receptor expression. CCR1, CCR2, CCR3, CCR5, CCR6 and CXCR3 are down-regulated within 6 h, while CCR7, CCR4, CCR8 and CXCR5 are up-regulated for 2 to 3 days. Up-regulation of CCR7 following TCR stimulation was observed also among resting peripheral blood T cells and required neither co-stimulation nor exogenous IL-2. On the other hand IL-2 down-regulated CXCR5, up-regulated CCR8 and facilitated the recovery of CCR3 and CCR5. Upon TCR stimulation, Th1 and Th2 cells produced comparable sets of chemokines, including RANTES, macrophage inflammatory protein-1beta, I-309, IL-8 and macrophage-derived chemokine, which may modulate surface chemokine receptors and contribute to cell recruitment at sites of antigenic recognition. Altogether these results show that following TCR stimulation effector/memory T cells transiently acquire responsiveness to constitutive chemokines. As a result, T cells that are activated in tissues may either recirculate to draining lymph nodes or migrate to nearby sites of organized ectopic lymphoid tissues.
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PMID:Switch in chemokine receptor expression upon TCR stimulation reveals novel homing potential for recently activated T cells. 1038 67

CXC chemokines play a important role in the process of leukocyte recruitment and activation at sites of inflammation. However, recent evidence suggests that these molecules can also regulate endothelial cell functions such as migration, angiogenesis and proliferation. In this study we have investigated CXC chemokine receptor expression in both primary cultures of human umbilical vein endothelial cells (HUVEC) and the spontaneously transformed HUVEC cell line, ECV304. We found that both cell types express mRNA for chemokine receptors CXCR1, CXCR2 and CXCR4, but not CXCR3. Flow cytometric analysis revealed low levels of CXCR1 but higher levels of CXCR4 cell surface expression. HUVECs responded to SDF-1alpha with a rapid and robust calcium flux, however no calcium flux was seen with either IL-8 or Gro-alpha. HUVECs and ECV304 cells did not proliferate in response to CXC chemokines, although ECV304 cells did migrate towards SDF-1alpha and IL-8. These data demonstrate that HUVECs and the endothelial cell line, ECV304 express functional CXC chemokine receptors.
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PMID:Cxc chemokine receptor expression on human endothelial cells. 1047 7

The importance of chemokine expression on HIV infection has been emphasized by the discovery that infection of CD4(+) T cells by M-tropic strains of HIV-1 is antagonized by the chemokines RANTES, MIP-1alpha, and MIP-1beta, which are natural ligands of CCR5, a major coreceptor for macrophagetropic (M-tropic) isolates of HIV-1. Similarly, the CCR2b ligands MCP-1 and MCP-3 inhibit productive infection of PBMCs by both CCR5- and CXCR4-dependent strains of HIV-1, suggesting that expression of the MCP-1 chemokine may affect HIV infection via signaling through the CCR2 receptor and subsequent desensitization of the CCR5 and/or CXCR4 signaling pathway. Given the major role played by chemokine receptors in HIV-1 fusion/entry and the regulatory effects of chemokines on HIV-1 infection, we examined the pattern of chemokine gene expression in HIV-1-infected myeloid cells and in primary monocyte/macrophages. Chronic HIV-1 infection of U937 monocytic cells increased the expression of RANTES, MIP-1alpha, MIP-1beta, and IL-8 chemokine genes, but strongly inhibited PMA/PHA- and TNFalpha-induced MCP-1 gene transcription. HIV-1-mediated inhibition of MCP-1 transcription and secretion was further confirmed in de novo HIV-1-infected U937 cells and correlated with a delay in HIV- and signal-induced NF-kappaB binding to the MCP-1 promoter. The inhibition of MCP-1 gene expression may provide a mechanism by which HIV-1 escapes the early influence of chemokine expression in monocytic cells.
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PMID:Differential regulation of CC chemokine gene expression in human immunodeficiency virus-infected myeloid cells. 1049 6

Mature mast cells are generally considered to be less mobile cells residing within tissue sites. However, mast cell numbers are known to increase in the context of inflammation, and mast cells are recognized to be important in regulating local neutrophil infiltration. CXC chemokines may play a critical role in this process. In this study two human mast cell-like lines, HMC-1 and KU812, and human cord blood-derived primary cultured mast cells were employed to examine role of stromal cell-derived factor-1 (SDF-1) in regulating mast cell migration and mediator production. It was demonstrated that human mast cells constitutively express mRNA and protein for CXCR4. Stimulation of human mast cells with SDF-1, the only known ligand for CXCR4, induced a significant increase in intracellular calcium levels. In vitro, SDF-1 alpha mediated dose-dependent migration of human cord blood-derived mast cells and HMC-1 cells across HUVEC monolayers. Although SDF-1 alpha did not induce mast cell degranulation, it selectively stimulated production of the neutrophil chemoattractant IL-8 without affecting TNF-alpha, IL-1beta, IL-6, GM-CSF, IFN-gamma, or RANTES production, providing further evidence of the selective modulation of mast cell function by this chemokine. These findings provide a novel, SDF-1-dependent mechanism for mast cell transendothelial migration and functional regulation, which may have important implications for the local regulation of mast cells in disease.
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PMID:Human mast cells transmigrate through human umbilical vein endothelial monolayers and selectively produce IL-8 in response to stromal cell-derived factor-1 alpha. 1086 Oct 54

The basis for the angiogenic effects of CXC chemokines such as interleukin 8 (IL-8) and for angiostatic chemokines such as interferon-inducible protein 10 (IP-10) has been difficult to assess. We recently reported, based on an RNase protection assay, that human umbilical vein endothelial cells (HUVECs) did not express detectable mRNA for the IL-8 receptors CXCR1 and CXCR2. This raised the possibility of heterogeneity of receptor expression by different endothelial cell (ECs) types. Since systemic angiogenesis induced by IL-8 would more likely involve microvessel ECs, we investigated CXC receptor expression on human microvascular dermal endothelial cells (HMECs). By confocal microscopy and immunofluorescence we observed that HMECs consistently expressed high levels of CXCR1 and CXCR4 (mean fluorescence intensity of 261+/-22.1 and 306.2+/-19, respectively) and intermediate levels of CXCR3 and CXCR2 (173.9+/-30. 2 and 156+/-30.9, respectively). In contrast, only a small proportion of HUVEC preparations expressed low levels of CXCR1, -2, and -3 (66+/-19.9; 49+/-15, and 81.4+/-17.9, respectively). However, both HMECs and HUVECs expressed equal levels of CXCR4. As expected, HMECs had more potent chemotactic responses to IL-8 than HUVECs, and this was correlated with the levels of IL-8 receptors on the ECs. Antibodies to CXCR1 and CXCR2 each had inhibitory effects on chemotaxis of HMECs to IL-8, indicating that both IL-8 receptors contributed to the migratory response of these cells toward IL-8. Assessment of the functional capacity of CXCR3 unexpectedly revealed that HMECs migrated in response to relatively higher concentrations (100-500 ng/ml) of each of the 'angiostatic' chemokines IP-10, ITAC, and MIG. Despite this, the 'angiostatic' chemokines inhibited the chemotactic response of HMECs to IL-8. IL-8 and SDF-1alpha but not IP-10 induced calcium mobilization in adherent ECs, suggesting that signaling events associated with calcium mobilization are separable from those required for chemotaxis. Taken together, our data indicated that functional differences among EC types is dependent on the level of the expression of CXC chemokine receptors. Whether this heterogeneity in receptor expression by ECs reflects distinct differentiation pathways remains to be established.
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PMID:Differential expression and responsiveness of chemokine receptors (CXCR1-3) by human microvascular endothelial cells and umbilical vein endothelial cells. 1102 90

Retinal pigment epithelial (RPE) cells form part of the blood-retina barrier and have recently been shown to produce various chemokines in response to proinflammatory cytokines. As the scope of chemokine action has been shown to extend beyond the regulation of leukocyte migration, we have investigated the expression of chemokine receptors on RPE cells to determine whether they could be a target for chemokine signaling. RT-PCR analysis indicated that the predominant receptor expressed on RPE cells was CXCR4. The level of CXCR4 mRNA expression, but not cell surface expression, increased on stimulation with IL-1beta or TNF-alpha. CXCR4 protein could be detected on the surface of 16% of the RPE cells using flow cytometry. Calcium mobilization in response to the CXCR4 ligand stromal cell-derived factor 1alpha (SDF-1alpha) indicated that the CXCR4 receptors were functional. Incubation with SDF-1alpha resulted in secretion of monocyte chemoattractant protein-1, IL-8, and growth-related oncogene alpha. RPE cells also migrated in response to SDF-1alpha. As SDF-1alpha expression by RPE cells was detected constitutively, we postulate that SDF-1-CXCR4 interactions may modulate the affects of chronic inflammation and subretinal neovascularization at the RPE site of the blood-retina barrier.
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PMID:CXCR4 receptor expression on human retinal pigment epithelial cells from the blood-retina barrier leads to chemokine secretion and migration in response to stromal cell-derived factor 1 alpha. 1103 74

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