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 chemokine beta family is comprised of at least six distinct cytokines that regulate trafficking of phagocytes and lymphocytes in mammalian species; at least one of these, macrophage inflammatory protein 1 alpha (MIP-1 alpha), also regulates the growth of hematopoietic stem cells. We now show that MIP-1 alpha and the related beta chemokine, RANTES, induce transient alterations in intracellular Ca2+ concentration in polymorphonuclear leukocytes that can be reciprocally and specifically desensitized, suggesting a common receptor. Moreover, we have now cloned both the cDNA and the gene for this receptor, functionally expressed the receptor in Xenopus oocytes, and mapped the gene to human chromosome 3p21. Transcripts for the receptor were found in mature and immature myeloid cells as well as B cells. The receptor is a member of the G protein-coupled receptor superfamily. It has approximately 33% amino acid identity with receptors for the alpha chemokine, interleukin 8, and may be the human homologue of the product of US28, an open reading frame of human cytomegalovirus.
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PMID:Structure and functional expression of the human macrophage inflammatory protein 1 alpha/RANTES receptor. 768 36

A number of cytokines have been implicated in the suppression of myeloid stem and progenitor cell proliferation. It has been suggested that some of these act directly on the stem/progenitors themselves, based on the effects of these cells, plated in culture at low seeding densities, on highly enriched populations. These studies, however, do not definitively rule out effects on accessory cells. To more rigorously evaluate direct-acting suppressive effects of cytokines, such cytokines were assessed for their effects on colony formation initiated by single bone marrow (BM) or umbilical cord blood (CB) CD34 cells sorted into single wells in the presence of a combination of growth-stimulating cytokines (erythropoietin [Epo], steel factor [SLF], granulocyte-macrophage colony-stimulating factor [GM-CSF], and interleukin-3 [IL-3]) and in the presence or absence of serum. Under these conditions, it was demonstrated that H-ferritin, transforming growth factor-beta 1 (TGF-beta 1), and members of the chemokine family (macrophage inflammatory protein-1 alpha [MIP-1 alpha], MIP-2 beta, platelet factor 4 [PF4], IL-8, and macrophage chemotactic and activating factor [MCAF]) had direct significant suppressive activities on single stem/progenitor cells from adult human BM in the presence or absence of serum. Single sorted CB cells were much less sensitive to inhibition by these cytokines. The reasons for this differential sensitivity are not known. Of possible relevance to this for cytokines, such as H-ferritin and the chemokines that have actions during S-phase of the cell cycle, CB progenitors were in slower cycle at initiation of culture than were BM progenitors.
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PMID:Comparative effects of suppressive cytokines on isolated single CD34(3+) stem/progenitor cells from human bone marrow and umbilical cord blood plated with and without serum. 769 34

Cytokine responses are dramatically affected when HIV-1 infected cells are activated with certain antigenic stimuli. We report the effects of HIV-1 tat gene in cytokine modulation, using HIV-1 tat transfected T (Jurkat) and B (Raji) cell lines. Studying the effect of tat and/or PMA + PHA on mRNA expression of 14 cytokines (IL-1 alpha, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, TNF-alpha, TNF-beta, GM-CSF, TGF-beta, IFN-gamma and MIP-1 alpha) illustrated differential effects. In addition to the varied effects of tat on the steady state levels of cytokine mRNAs, tat induced the secretion of TNF-beta preferentially in both B and T cell lines, either by itself as in Raji B cell line or synergistically upon PMA + PHA stimulation as in Jurkat T cell line.
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PMID:Differential expression of cytokine genes in HIV-1 tat transfected T and B cell lines. 769 26

Specific cell recruitment to a site of acute inflammation is a crucial event characterized by the elicitation of mainly polymorphonuclear neutrophils (PMNs). Recently, it has been reported that PMNs can express and secrete chemotactic cytokines or chemokines, including IL-8, MIP-1 alpha, and MIP-1 beta. Moreover, PMN-derived chemokines are regulated by various soluble mediators, such as dexamethasone, prostaglandin E, classic chemoattractant factors (e.g., fMLP, C5a, leukotriene B4), IL-4, and IL-10. In this article we demonstrate that PMNs treated with IFN-gamma, a Th1-derived cytokine, can inhibit early mRNA expression for MIP-1 alpha, MIP-1 beta, and IL-8 (up to 8 hours post IFN-gamma addition), while augmenting their production at 24 hours post IFN-gamma addition. Furthermore, our studies demonstrate that one of the mechanisms for the activity of IFN-gamma in this system is via the autocrine activity of TNF-alpha. These data imply that PMN-derived chemokines are regulated by not only proinflammatory cytokines, including IL-1 beta and TNF-alpha, but also Th1- and Th2-derived cytokines, including IL-4, IL-10, and IFN-gamma. The role of these cytokine networks in regulating PMN-derived chemokines may play an important role in leukocyte elicitation during the initiation and maintenance of an inflammatory response.
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PMID:Interferon gamma modulates the expression of neutrophil-derived chemokines. 771 60

Cells of the osteoblastic lineage play a major role in the regulation of osteoclastic bone resorption. Recent studies have demonstrated production of chemokines by osteoblastic cells. Although these phagocyte-stimulating and proinflammatory cytokines act as chemoattractants and activators for other members of the hemopoietic lineage, their actions on osteoclasts have not been characterized. We found that macrophage inflammatory protein-1 alpha (MIP-1 alpha) and IL-8 inhibited bone resorption by rat osteoclasts, primarily through reduction in the proportion of osteoclasts resorbing bone, a pattern of inhibition previously observed in response to macrophage CSF (M-CSF). MIP-2, RANTES, MIP-1 beta, and monocyte chemotactic protein-1 were without effect on resorption. MIP-1 alpha and IL-8, but not the other chemokines, also stimulated osteoclastic motility and increased the osteoclast spread area in a dose-dependent manner, over the same concentration range as that which inhibited bone resorption. In addition, MIP-1 alpha induced osteoclast orientation in a gradient of the chemokine, and stimulated osteoclast migration. We detected no effect of chemokines on osteoclast formation or survival. Our data suggest that chemokines can promote osteoclast orientation and migration, processes that might be involved in chemotaxis; it seems appropriate that resorptive functions should be suppressed during migration. Because chemokines are proinflammatory, their actions on osteoclasts might represent mechanisms by which bone resorption is modulated by the inflammatory process when this occurs in bone. However, given that chemokines are increasingly recognized to be multifunctional and that they are produced by cells of the osteoblastic lineage, they may also be components of the physiologic regulation of bone resorption.
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PMID:Macrophage inflammatory protein-1 alpha and IL-8 stimulate the motility but suppress the resorption of isolated rat osteoclasts. 775 48

In two lines of transgenic rats (pX rats) from WKAH and F344 strains and carrying the human T-lymphotropic virus type I pX gene, undifferentiated mammary carcinomas developed predominantly in females starting at about 5 months of age, and there was massive infiltration of granulocytes in the tumor tissue. The incidence of the tumor reached about 40% when the rats were 12 months old. mRNAs of both pX and host genes Gro and MIP-2, which are granulocyte chemoattractants of the interleukin 8 family, were highly expressed in the tumor tissue. Since expression and point mutation of several oncogenes and the antioncogene were not demonstrated, hitherto unidentified novel oncogenic pathways may be transactivated by the pX transgene in these pX rats.
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PMID:Cytokine-producing mammary carcinomas in transgenic rats carrying the pX gene of human T-lymphotropic virus type I. 778 Sep 62

Macrophages, within the cytokine network, are a major source of many cytokines involved in immune response, hematopoiesis, inflammation and many other homeostatic processes. Upon stimulation by micro-organisms, microbial products or endogenous factors including cytokines, macrophages can de novo synthesize and release a large variety of cytokines (ie IL-1, IL-1ra, IL-6, IL-8, IL-10, IL-12, TNF alpha, IFN alpha, IFN gamma, MCP-1, MCP-3, MIF, M-CSF, G-CSF, GM-CSF, MIP-1, MIP-2, LIF, OSM, TGF beta). Some cytokines can upregulate the production of cytokines by macrophages (IL-3, GM-CSF, IFN gamma) while others can inhibit it (IL-4, IL-10, IL-13, TGF beta). In addition, these cytokines can modulate most of the macrophage functions and cell surface marker expression. Other cytokines (the chemokines such as MCP-1,2,3, MIP-1,2 and RANTES) contribute to the recruitment of circulating monocytes within tissues. It is worth noting that macrophages can be their own source of regulatory cytokines.
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PMID:Cytokines and macrophages. 785 54

We have demonstrated that the orphan receptor representing the putative mouse (mu) homolog of the human (hu) interleukin-8 receptor beta (IL-8R beta) binds the mouse N51 cytokine, also known as KC. The muIL-8R beta gene was constitutively expressed in NIH 3T3 cells (NIH-muIL-8R beta). Cells and plasma membranes from the NIH-muIL-8R beta clone showed binding of 125I-N51 that was displaced by unlabeled N51. Other related cytokines were assayed for their ability to displace 125I-N51. MIP-2 and GRO alpha/MGSA competed as well as N51 for the receptor, but huIL-8 and NAP-2 did not compete at all. Chimeric molecules between IL-8 and N51 were used to extend the binding analysis. The segment between the conserved cysteines 2 and 3, named domain I; cysteines 3 and 4, domain II; and cysteine 4 and the C terminus, domain III of IL-8 were replaced by the corresponding domains of N51 and vice versa. When studying the binding of 125I-N51 and the hybrid molecules to the receptor, we observed that chimeras of N51 containing either domain I, II, or III of IL-8 were agonists of N51, and chimeras of IL-8 containing domain II or III of N51 were partial agonists of N51. These results demonstrate that domain I of N51 does not confer binding specificity and suggest that the region from the third cysteine to the C terminus of the N51 molecule is more important for binding to muIL-8R beta.
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PMID:The orphan mouse receptor interleukin (IL)-8R beta binds N51. Structure-function analysis using N51/IL-8 chimeric molecules. 789 Jun 4

We have examined the ligand specificity and signal transduction pathways of a recently cloned receptor for monocyte chemoattractant protein-1 (MCP-1). In human 293 cells stably transfected with the MCP-1 receptor, MCP-1 bound specifically with high affinity (Kd = 260 pM) and induced a rapid mobilization of calcium from intracellular stores. The closely related chemokines MIP-1 alpha, MIP-1 beta, RANTES, interleukin 8 (IL-8), and Gro-alpha were inactive at concentrations as high as 300 nM. Activation of the MCP-1 receptor potently inhibited adenylyl cyclase with an IC50 = 90 pM. Activation of the MIP-1 alpha/RANTES receptor also mediated inhibition of adenylyl cyclase activity but with a different pharmacological profile: MIP-1 alpha (110 pM, IC50), RANTES (140 pM), MIP-1 beta (10 nM), and MCP-1 (820 nM). Mobilization of intracellular calcium and inhibition of adenylyl cyclase were blocked by pertussis toxin, suggesting that the MCP-1 receptor coupled to G alpha i. These results demonstrate that the MCP-1 receptor binds and signals in response to picomolar concentrations of MCP-1 in a highly specific manner. Signaling was manifested as mobilization of intracellular calcium and inhibition of adenylyl cyclase and was mediated by a pertussis toxin-sensitive G-protein(s).
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PMID:Signal transduction and ligand specificity of the human monocyte chemoattractant protein-1 receptor in transfected embryonic kidney cells. 789 Jul 8

To date no hematopoietic progenitors of dendritic Langerhans' cells (DLC), which represent an highly efficient class of antigen presenting cells, have been identified or the cytokines they elaborate have been defined. Here we describe an acute leukemia patient whose blasts (90-96% in peripheral blood and bone marrow) had a phenotype consistent with putative progenitors of DLC. The patient was treated with ara-C and VP-16 but did not achieve remission. The blasts had lobulated nuclei, no cytoplasmic vacuolation or Auer rods and were weakly positive for acid phosphatase and non-specific esterase and negative for PAS, granzyme A, dipeptidyl aminopeptidase IV, ATPase/ADPase and lysozyme production. The blasts were positive for CD1a, CD4, CD16, CD35, HLADR, HLADQ, CD11b, CD11c, CD14, CD33, CD34, CD11a, CD71, CD19, CD25, IL-2R beta and negative for CD2, CD7, CD8, CD10, CD22, CD56, CD57, surface or cytoplasmic CD3, TCR delta and TCR beta, HTLV-1p19 and P-glycoprotein. On liquid culture with or without 5 x 10(-9) M 12-O-tetradecanoylphorbol-13-acetate (TPA) for 3 days, the blasts formed aggregates of proliferating and elongating cells on the wall of the flasks with a decline in CD34, numerous dendritic processes appeared on the cells and there was strong positivity for ATPase/ADPase, but no other changes in phenotype. No macrophages were observed, indicating derivation from separate DLCs. Cytogenetic analysis showed chromosomal abnormalities and electron microscopy showed Birbeck granules. Southern blotting of DNA showed rearrangement of one allele for both JH and TCR beta but no HTLV-1 related sequences. Culture supernatants from blasts cultured with or without TPA showed the production of large amounts of IL-8, IL-6, TNF-alpha, MIP-1 alpha, IL-10 and interferon gamma and modest amounts of IL-1 alpha, GM-CSF and stem cell factor. The presence not only of CD1a, HLADR, HLADQ and many other characteristics including Birbeck granules, but also differentiation along the lines of DLC with appearance of dendritic processes on the cells and expression of ATPase/ADPase activity, indicate that the leukemic blasts in our patient represented a leukemic counterpart of normal progenitors of DLC and the leukemia a new entity which could possibly be classified as AML-M8. Lastly, many pro-inflammatory cytokines produced by DLC could contribute to inflammation and IL-10 to immunosuppression.
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PMID:Phenotype, genotype and cytokine production in acute leukemia involving progenitors of dendritic Langerhans' cells. 791 55


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