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)

Macrophage inflammatory protein (MIP)-1 alpha, part of a family termed chemokines, has been implicated in suppression of hemopoietic stem and progenitor cell proliferation. The chemokine family has been organized into two subgroups with MIP-1 alpha, MIP-1 beta, macrophage chemotactic and activating factor (MCAF) and RANTES belonging to one subgroup, and GRO-alpha, MIP-2 alpha (GRO-beta), MIP-2 beta (GRO-gamma), platelet factor 4 (PF4), IL-8, and neutrophil activating peptide (NAP)-2 belonging to the other. These molecules were evaluated for effects on colony formation by human bone marrow multipotential (CFU-GEMM), erythroid (BFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells. None of the chemokines stimulated colony formation in the absence of CSF, or influenced colony formation stimulated by a single growth factor such as granulocyte-macrophage-CSF or erythropoietin. However, MIP-1 alpha, MIP-2 alpha, PF4, IL-8, and MCAF suppressed in dose-response fashion colony formation of immature subsets of myeloid progenitor cells stimulated by GM-CSF plus steel factor. Effects were apparent on low density and CD34 HLA-DR(+)-sorted marrow cells in which up to 88.4% of the cells were composed of progenitor cells, suggesting direct effects on the progenitors themselves. Up to 2500-fold less of each chemokine could be used to demonstrate synergistic suppression when any two of these five chemokines were used together at low concentrations, effects also apparently directly on the progenitors. In contrast, MIP-1 beta, MIP-2 beta, GRO-alpha, NAP-2, and RANTES were not suppressive nor did they synergize with MIP-1 alpha, MIP-2 alpha, PF4, IL-8, or MCAF to suppress. However, a fivefold excess of MIP-1 beta blocked the suppressive effects of MIP-1 alpha. Similarly, a fivefold excess of either MIP-2 beta or GRO-alpha blocked the suppressive effects of IL-8 and PF4. These suppressing, synergizing and blocking effects may be of relevance to blood cell regulation.
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PMID:Comparative analysis of the human macrophage inflammatory protein family of cytokines (chemokines) on proliferation of human myeloid progenitor cells. Interacting effects involving suppression, synergistic suppression, and blocking of suppression. 768 42

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

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

Macrophage-stimulating protein (MSP), originally identified as an inducer of murine resident macrophage responsiveness to chemoattractants, is a ligand for human RON/murine STK receptor protein tyrosine kinases. Since STK was cloned from populations enriched for hematopoietic stem cells, we initiated studies on the effects of MSP on colony formation by granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) myeloid progenitor cells. MSP alone had no colony stimulating activity. However, MSP caused about a 50% suppression of CFU-GM colony formation induced by synergistic combinations of SLF or Flt-L plus GM-CSF, G-CSF, or IL-3 and of BFU-E and CFU-GEMM colonies induced by SLF or Flt3-L plus Epo or Epo and IL-3. In contrast, MSP had no effect on progenitors stimulated by one growth factor. MSP also suppressed colony formation by stimulated cord blood progenitors, but only after preinduction to a rapidly cycling state. It was previously reported that several members of the chemokine family synergistically suppress myeloid progenitor proliferation. Likewise, synergistic suppression was observed when MSP was paired with VEGF, MIP-1 alpha, IL-8, PF4, MCP-1, IP-10, or ENA-78, or when VEGF was paired with the chemokines; and the required MSP concentration was more than 100-fold less than for MSP alone. Additionally, MSP or VEGF inhibited proliferation of the human myeloid growth factor-dependent cell line, M07e, but a sustained effect required multiple additions over time. At the least, some of the MSP suppressive effects on myeloid progenitors, as assessed on single isolated CD34 marrow cells, appeared to be directly on the progenitors; sustained additions of MSP were required to see this effect. The suppressive action of MSP and its synergism with proteins of the chemokine family may be of relevance to regulation of blood cell production.
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PMID:Macrophage-stimulating protein, a ligand for the RON receptor protein tyrosine kinase, suppresses myeloid progenitor cell proliferation and synergizes with vascular endothelial cell growth factor and members of the chemokine family. 869 17

Over a period of 14 days a longitudinal analysis was performed on the effects of filgrastim (recombinant human granulocyte colony stimulating factor, rhG-CSF) administered to 20 postoperative/posttraumatic patients at risk of or with sepsis. The following parameters were determined: leukocyte counts, serum cytokine levels and the surface expression of functional antigens and adhesion molecules. Filgrastim (1 mu g/kg.day) was infused continuously on the first 3 days and tapered to 0.5 mu g/kg.day on the following 4 days or until discharge from the surgical intensive care unit. During infusion of filgrastim, G-CSF levels increased in 16 out of the 20 patients within 48 h. In these 16 patients, leukocyte counts increased in 15 out of 16 patients. Expression of CD64 was upregulated within 24 h. The expression of CD32 was upregulated in 8 out of 9 patients with an initial expression < 55%. LAM-1 expression was downregulated in all patients revealing an initial expression of LAM-1 > 40%. Soluble ICAM increased in 9 out of 11 patients. IL-8 decreased in all 6 patients presenting initial values of IL-8 > 90 pg/ml. IL-1RA increased in 10 patients. Filgrastim had no effect on the expression of CD14, CD16 and CD34 and on the levels of TNF-alpha and sTNF-R type I (p55). In conclusion, infusion of filgrastim in postoperative/post traumatic patients at risk of and with sepsis resulted in improved generation and function of neutrophils and appeared to counterregulate hyperactivation of proinflammatory processes.
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PMID:Filgrastim (RHG-CSF) related modulation of the inflammatory response in patients at risk of sepsis or with sepsis. 883 41

In a serum-free liquid culture, thrombopoietin (TPO) selectively stimulated the growth of megakaryocytic cells from CD34-positive cord blood cells. Using these cultured cells, we investigated cytokine production by human megakaryocytes. Day 10 megakaryocytes (2 x 10(5)) secreted > 1000 pg/ml of interleukin (IL)-8, in contrast to small amounts of IL-1beta and IL-6. A time-course study showed that the IL-8 production of megakaryocytes occurred at the late phase of the culture period. The megakaryocyte-conditioned medium had the chemotactic potential of polymorphonuclear leucocytes, which was abrogated by the addition of anti-IL-8 antibody, suggesting the secretion of biologically active IL-8. The combination of TPO and IL-1alpha was required for a significant augmentation of the IL-8 secretion. Direct evidence for IL-8 synthesis in megakaryocytes was provided by reverse transcription-polymerase chain reaction on purified CD41b+ cells and by the detection of intracellular IL-8 in CD41b+ cells. These results suggest that TPO stimulates not only the proliferation and differentiation of the progenitors capable of megakaryocytic lineage expression but also IL-8 release by the megakaryocytic cells with the aid of IL-1.
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PMID:Megakaryocytes derived from CD34-positive cord blood cells produce interleukin-8. 940 Oct 57

Interleukin (IL)-8 is a multifunctional cytokine that can stimulate the division of endothelial cells. We examined the expression of IL-8 mRNA using Northern blot analysis and in situ mRNA hybridization (ISH) and protein production using enzyme-linked immunosorbent assay and immunohistochemistry in 8 human gastric carcinoma cell lines and 39 gastric carcinomas and corresponding normal mucosa (34 surgical specimens and 5 biopsy specimens). Of the 8 human gastric carcinoma cell lines, 6 expressed 1.8-kb IL-8 mRNA and secreted various levels of IL-8 protein. The expression of IL-8 by TMK-1 cells was induced by exposure to IL-1 alpha, epidermal growth factor, and transforming growth factor-alpha, shown previously to be autocrine growth stimulators for human gastric carcinoma cells. In tumor tissues, most of the tumors (28 of 34 surgical specimens and 4 of 5 biopsy specimens) expressed IL-8 at higher levels than the corresponding normal mucosa. ISH and immunohistochemical analyses revealed that IL-8 mRNA and protein were localized in the cytoplasm of tumor cells. The number of blood vessels in the gastric carcinomas was determined by using antibodies against CD34. The level of IL-8 mRNA in the neoplasms strongly correlated with vascularization (Spearman correlation, r = 0.812; P = 0.001). The data suggest that IL-8 produced by tumor cells may regulate neovascularization and, hence, the growth and spread of human gastric carcinoma.
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PMID:Expression of interleukin-8 correlates with vascularity in human gastric carcinomas. 942 27

The mechanism(s) underlying the release of stem/progenitor cells from bone marrow into the circulation is poorly understood. We hypothesized that matrix metalloproteinases (MMPs), especially gelatinases, which are believed to participate in the proteolysis of basement membranes and in the migration of leukocytes, may facilitate this process. First, we investigated whether CD34(+) stem/progenitor cells express gelatinases A (MMP-2) and/or B (MMP-9) and whether growth factors and cytokines (granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], stem cell factor [SCF], macrophage colony-stimulating factor [M-CSF], interleukin-3 [IL-3], IL-6, IL-8, and tumor necrosis factor-alpha [TNF-alpha]) are able to modulate their expression. Next, we examined the transmigration of these stem/progenitor cells through reconstituted basement membrane (Matrigel) and its modulation by growth factors and cytokines. CD34(+) cells were obtained from steady-state bone marrow and peripheral blood (from leukapheresis products collected either in steady-state hematopoiesis or after mobilization with G-CSF plus chemotherapy or G-CSF alone). We found that peripheral blood CD34(+) cells, regardless of whether they were mobilized or not, strongly expressed both gelatinases (MMP-2 and MMP-9) in contrast to steady-state bone marrow CD34(+) cells, which did not. However, all the growth factors and cytokines tested could induce MMP-2 and MMP-9 secretion by the latter cells. Moreover, the stimulatory effects of G-CSF and SCF on both MMP-2 and MMP-9 secretion were found to be significantly higher in CD34(+) cells isolated from bone marrow than in those from peripheral blood. In addition TNF-alpha, GM-CSF, and IL-6 increased the secretion of a partially active form of MMP-2. Basal transmigration of bone marrow CD34(+) cells through Matrigel was lower than that of peripheral blood CD34(+) cells (P <.0001), but growth factors and cytokines increased it by 50% to 150%. Positive correlations were established between expression of gelatinases and CD34(+) cell migration (r >.9). The stimulatory effect of G-CSF was significantly greater on the migration of CD34(+) cells from bone marrow than on those from peripheral blood (P =.004). Moreover, CD34(+) cell migration was reduced to approximately 50% by antibodies to MMP-2 and MMP-9, tissue inhibitors of metalloproteinases (rhTIMP-1 and -2), and o-phenanthroline. TNF-alpha-induced gelatinase secretion and migration of CD34(+) cells and of clonogenic progenitors (colony-forming unit-granulocyte-macrophage [CFU-GM], burst-forming unit-erythroid [BFU-E], colony-forming unit granulocyte, erythroid, monocyte, megakaryocyte [CFU-GEMM], and colony-forming unit-megakaryocyte [CFU-MK]) were dose-dependent. Therefore, this study demonstrated that CD34(+) cells that are circulating in peripheral blood express both MMP-2 and MMP-9 and transmigrate through Matrigel. In contrast, CD34(+) cells from steady-state bone marrow acquire similar properties after exposure to growth factors and cytokines, which upregulate expression of gelatinases and transmigration of these cells when they enter the bloodstream. Hence, we suggest that growth factors and cytokines induce release of stem/progenitor cells from bone marrow into peripheral blood during mobilization, as well as during steady-state hematopoiesis, by signaling through gelatinase pathways.
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PMID:Growth factors and cytokines upregulate gelatinase expression in bone marrow CD34(+) cells and their transmigration through reconstituted basement membrane. 1023 90

To clarify the roles of megakaryocytes and platelets in the responses associated with infection and inflammation, we examined the effects of interleukin (IL) 1, the common mediator of the inflammatory process, on the development and secretory functions of megakaryocytes generated from CD34(+)cord blood cells under stimulation with thrombopoietin (TPO). The addition of IL-1alpha did not influence the generation, endomitosis or expression of surface makers of megakaryocytes, compared with TPO alone. However, IL-1alphaenhanced the ability of megakaryocytes to produce IL-8 and growth-regulating oncogene-alpha(GRO-alpha) in the presence of TPO. In contrast, the production of regulated on activation with normal T cell expressed and secreted (RANTES), platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG) were not potentiated. A flow cytometric analysis and a reverse transcription-polymerase chain reaction analysis revealed IL-1 receptor type I (IL-1RI) expression of megakaryocytes generated by TPO. Moreover, the addition of an anti-IL-1RI monoclonal antibody significantly decreased the TPO plus IL-1alpha-induced secretion of IL-8 by the cultured megakaryocytes to the level attained by TPO alone. These results suggest that the production of IL-8 and GRO-alpha (but not RANTES), PF4 and beta-TG, by megakaryocytes is potentiated by signalling through IL-1RI with the aid of TPO. Thus, megakaryocytes and platelets may play an important role in the development of inflammation via chemokine release.
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PMID:Chemokine production by human megakaryocytes derived from CD34-positive cord blood cells. 1034 82

The aim of this study was to explore further the hypothesis that early stages of normal human hematopoiesis might be coregulated by autocrine/paracrine regulatory loops and by cross-talk among early hematopoietic cells. Highly purified normal human CD34(+) cells and ex vivo expanded early colony-forming unit-granulocyte-macrophage (CFU-GM)-derived, burst forming unit-erythroid (BFU-E)-derived, and CFU-megakaryocyte (CFU-Meg)-derived cells were phenotyped for messenger RNA expression and protein secretion of various growth factors, cytokines, and chemokines to determine the biological significance of this secretion. Transcripts were found for numerous growth factors (kit ligand [KL], FLT3 ligand, fibroblast growth factor-2 [FGF-2], vascular endothelial growth factor [VEGF], hepatocyte growth factor [HGF], insulinlike growth factor-1 [IGF-1], and thrombopoietin [TPO]); cytokines (tumor necrosis factor-alpha, Fas ligand, interferon alpha, interleukin 1 [IL-1], and IL-16); and chemokines (macrophage inflammatory protein-1alpha [MIP-1alpha], MIP-1beta, regulated upon activation, normal T cell expressed and secreted [RANTES], monocyte chemotactic protein-3 [MCP-3], MCP-4, IL-8, interferon-inducible protein-10, macrophage-derived chemokine [MDC], and platelet factor-4 [PF-4]) to be expressed by CD34(+) cells. More importantly, the regulatory proteins VEGF, HGF, FGF-2, KL, FLT3 ligand, TPO, IL-16, IGF-1, transforming growth factor-beta1 (TGF-beta1), TGF-beta2, RANTES, MIP-1alpha, MIP-1beta, IL-8, and PF-4 were identified in media conditioned by these cells. Moreover, media conditioned by CD34(+) cells were found to inhibit apoptosis and slightly stimulate the proliferation of other freshly isolated CD34(+) cells; chemo-attract CFU-GM- and CFU-Meg-derived cells as well as other CD34(+) cells; and, finally, stimulate the proliferation of human endothelial cells. It was also demonstrated that these various hematopoietic growth factors, cytokines, and chemokines are expressed and secreted by CFU-GM-, CFU-Meg-, and BFU-E-derived cells. It is concluded that normal human CD34(+) cells and hematopoietic precursors secrete numerous regulatory molecules that form the basis of intercellular cross-talk networks and regulate in an autocrine and/or a paracrine manner the various stages of normal human hematopoiesis.
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PMID:Numerous growth factors, cytokines, and chemokines are secreted by human CD34(+) cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine/paracrine manner. 1134 33

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