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)

Nontransformed stromal colony-derived cell lines (CDCLs) consist of a pure stromal cell population that differentiates following a vascular smooth muscle cell repertoire, and whose in vivo counterpart is that of myoid cells found in adult and fetal human bone marrow cords. We studied the cytokine expression by reverse-transcriptase polymerase chain reaction (RT-PCR) from pooled fast-growing clones from 10 different bone marrow samples. RT-PCR indicated that 30 cytokines (out of 42 studied) were expressed by CDCLs (20 after medium renewal and hydrocortisone renewal, three after addition of interleukin I beta (IL-1 beta) and seven in only part of the CDCL layers examined). The cytokines expressed comprised mediators known to be involved in the maintenance of early and late hematopoiesis (IL-1 alpha and IL-beta, IL-6, IL-7, IL-8, IL-11 and IL-13; colony-stimulating factors, thrombopoietin, erythropoietin, stem cell factor, fit 3-ligand, hepatocyte cell growth factor, tumor necrosis factor alpha, leukemia inhibitory factor, transforming growth factors beta 1 and beta 3; and macrophage inflammatory protein 1 alpha), angiogenic factors (fibroblast growth factors 1 and 2, vascular endothelial growth factor) and mediators whose usual target (and source) is the connective tissue-forming cells (platelet-derived growth factor A, epidermal growth factor, transforming growth factors alpha and beta 2, oncostatin M and insulin-like growth factor 1), or neuronal cells (nerve growth factor). The cytokines not expressed were lymphokines (IL-2, IL-3, IL-4, IL-5, IL-9, IL-10, and IL-12 and interferon gamma) or mediators synthesized by macrophages (inhibin, activin, platelet-derived growth factor B, and IL-1 receptor antagonist). This study complements the description of the phenotype of the myoid cells, confirming that these cells are the marrow connective tissue-forming cells; moreover, this work suggests that stromal control of hematopoiesis is multifactorial and that myoid cells are involved in the control of marrow angiogenesis and innervation.
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PMID:The broad spectrum of cytokine gene expression by myoid cells from the human marrow microenvironment. 909 Jul 90

Thrombopoietin (TPO) regulates early and late stages of platelet formation as well as platelet activation. TPO exerts its effects by binding to the receptor, encoded by the protooncogene c-mpl, that is expressed in a large number of cells of hematopoietic origin. In this study, we evaluated the expression of c-Mpl and the effects of TPO on human polymorphonuclear cells (PMN). We demonstrate that PMN express the TPO receptor c-Mpl and that TPO induces STAT1 tyrosine phosphorylation and the formation of a serum inducible element complex containing STAT1. The analysis of biological effects of TPO on PMN demonstrated that TPO, at concentrations of 1-10 ng/ml, primes the response of PMN to n-formyl-met-leu-phe (FMLP) by inducing an early oxidative burst. TPO-induced priming on FMLP-stimulated PMN was also detected on the tyrosine phosphorylation of a protein with a molecular mass of approximately 28 kD. Moreover, we demonstrated that TPO by itself was able to stimulate, at doses ranging from 0.05 to 10 ng/ml, early release and delayed synthesis of interleukin 8 (IL-8). Thus, our data indicate that, in addition to sustaining megakaryocytopoiesis, TPO may have an important role in regulating PMN activation.
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PMID:Regulation of polymorphonuclear cell activation by thrombopoietin. 912 1

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

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 regulation of megakaryocytopoiesis and thrombopoiesis appears to be under the control of an array of hematopoietic growth factors. To determine the relationship between endogenous cytokine levels and circulating platelet counts, we measured the serum levels of both thrombopoietic and inflammatory cytokines in the peripheral blood and bone marrow samples from 70 patients with clonal thrombocytosis (CT) caused by myeloproliferative disorders, 28 patients with reactive thrombocytosis (RT), and 35 normal control subjects. The levels of thrombopoietin (TPO), interleukin-6 (IL-6), soluble IL-6 (sIL-6) receptor, IL-11, stem cell factor (SCF), IL-3, and IL-8 were determined by enzyme-linked immunosorbent assay (ELISA). Platelet counts were significantly higher in both CT and patients with RT (699+/-399x10(9)/L, P<.001; 642+/-200 x 10(9)/L, P<.001; respectively) as compared with the normal control subjects (240+/-47x10(9)/L). The concentrations of cytokines in the bone marrow correlated well with those in the peripheral blood. The endogenous levels of TPO, IL-6, and sIL-6 receptor were significantly higher in both CT and patients with RT than those in normal control subjects. The median level of IL-6 was significantly higher in patients with RT than in patients with CT (40 pg/mL vs. 5 pg/mL; P<.001); however, there was no detectable difference in TPO and sIL-6 receptor levels between the two groups. Significantly higher levels of SCF and IL-8 were also found in patients with CT as compared with those found in normal control subjects (median 2460 pg/mL vs 1995 pg/mL, P<.05; 20 ng/mL vs. 5 ng/mL, P = .001; respectively). Finally, IL-11 and IL-3 levels were undetectable in most patients with thrombocytosis. Our results reveal that the endogenous levels of TPO, IL-6, sIL-6 receptor, IL-8, and SCF are elevated in patients with CT or RT. These cytokines appear to be active mediators involved in the regulation of thrombopoiesis during clonal and reactive thrombocytosis.
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PMID:Circulating levels of thrombopoietic and inflammatory cytokines in patients with clonal and reactive thrombocytosis. 1052 Oct 86

Stem cell trafficking between extravascular marrow sites and circulating blood is an essential part of the blood stem cell transplantation technology. Recombinant human G-CSF (rHuG-CSF) is widely used for stem cell peripheralization alone or together with chemopriming mobilizing early and pluripotent CD34+ cell subsets. New cytokine/chemokine mobilization regimens are under investigation such as combined rHuG-CSF and rHu thrombopoietin, rHuG-CSF and interleukin 3, rHuG-CSF and rHu stem cell factor, rHuG-CSF and Flt-3 ligand, human macrophage inflammatory protein, interleukin 1, and interleukin 8. Modifying the adherence of CD34+ cells to extracellular matrix molecules is a new mechanism by which hematopoietic progenitor cells are released into the circulating blood. Blocking the alpha4beta1 integrin receptor on CD34+ progenitor cells by using monoclonal antibodies specific for the heterodimeric complex alpha4beta1 has been shown to further increase the circulating stem cell concentration when given following rHuG-CSF priming. The current clinical research is primarily focused on improving stem cell mobilization efficiency in heavily pretreated and poorly mobilizing patients, and to decrease adverse effects of cytokine treatment.
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PMID:In vivo expansion of the circulating stem cell pool. 1101 55

Paclitaxel and carboplatin chemotherapy is reported to be a platelet-sparing drug combination. This study investigated potential mechanisms for this observation by studying the effects of paclitaxel and carboplatin on (1) normal donor and chemotherapy patient-derived erythroid (burst-forming units-erythroid [BFU-E]), myeloid (colony-forming units-granulocyte/macrophage [CFU-GM]), and megakaryocyte (CFU-Meg) progenitor cell growth; (2) P-glycoprotein (P-gp) protein and glutathione S-transferase (GST) messenger RNA (mRNA) expression; (3) serum thrombopoietin (Tpo), stem cell factor (SCF), interleukin-6 (IL-6), IL-11, IL-1beta, IL-8, and tumor necrosis factor-alpha levels in patients treated with paclitaxel and carboplatin; and (4) stromal cell production of Tpo and SCF after paclitaxel and carboplatin exposure. CFU-Meg were more resistant to paclitaxel alone, or in combination with carboplatin, than CFU-GM and BFU-E. Although all progenitors expressed P-gp protein and GST mRNA, verapamil treatment significantly, and selectively, increased the toxicity of paclitaxel and carboplatin to CFU-Meg, suggesting an important role for P-gp in megakaryocyte drug resistance. Compared to normal controls, serum Tpo levels in patients receiving paclitaxel and carboplatin were significantly elevated 5 hours after infusion and remained elevated at day 7 (287% +/- 63% increase, P <.001). Marrow stroma was shown to be the likely source of this Tpo. It is concluded here that P-gp-mediated efflux of paclitaxel, and perhaps GST-mediated detoxification of carboplatin, results in relative sparing of CFU-Meg, which may then respond to locally high levels of stromal cell-derived Tpo. The confluence of these events might lead to the platelet-sparing phenomenon observed in patients treated with paclitaxel and carboplatin chemotherapy.
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PMID:Investigating the platelet-sparing mechanism of paclitaxel/carboplatin combination chemotherapy. 1115 79

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

Although being largely used for pathobiological models of cartilage diseases such as osteoarthritis (OA), human chondrocytes are still enigmatic cells, in as much as a large part of their secretome is unknown. We took advantage of the recent development of antibody-based microarrays to study multiple protein expression by human chondrocytes obtained from one healthy and five osteoarthritic joints, in unstimulated conditions or after stimulation by the proinflammatory cytokines interleukin-1 (IL-1) or tumour necrosis factor (TNF). The secretion media of chondrocytes were incubated with array membranes consisting of 79 antibodies directed against cytokines, chemokines, and angiogenic or growth factors. Several proteins were identified as new secretion products of chondrocytes, including the growth or angiogenic factors EGF, thrombopoietin, GDNF, NT-3 and -4, and PlGF, the chemokines ENA-78, MCP-2, IP-10, MIP-3alpha, NAP-2, PARC, and the cytokines MIF, IL-12, and IL-16. Most of the newly identified chemokines were increased intensely after stimulation by IL-1 or TNF, as for other proteins of the array, including GRO proteins, GM-CSF, IL-6, IL-8, MIP-1beta, GCP-2, and osteoprotegerin. The up-regulation by cytokines suggested that these proteins may participate in the destruction of cartilage and/or in the initiation of chemotactic events within the joint during OA. In conclusion, the microarray approach enabled to unveil part of an as yet unexplored chondrocyte secretome. Our findings demonstrated that chondrocytes were equipped with a proinflammatory arsenal of proteins which may play an important part in the pathogenesis of OA and/or its drift towards an inflammatory, rheumatoid phenotype.
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PMID:The inflammatory side of human chondrocytes unveiled by antibody microarrays. 1538 Oct 94

Angiogenesis plays an important role in solid tumors and hematologic malignancies. The prognostic significance of angiogenic factors in adult acute lymphoblastic leukemia (ALL) remains ambiguous. We therefore analyzed the impact of angiogenic factor levels on overall survival of newly diagnosed adult ALL patients. Plasma levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), interleukin-1 receptor alpha (IL-1Ralpha), IL-6, IL-8, VEGF receptors VEGFR1 and VEGFR2, and thrombopoietin (TPO) were measured in plasma samples of 95 patients by enzyme-linked immunosorbent assay (ELISA). In a univariate Cox proportional hazards model, higher levels of IL-1Ralpha, IL-8, VEGFR1, and VEGFR2 were predictive of poor survival. In contrast, higher levels of VEGF were predictive of longer survival, and higher levels of bFGF suggested a similar trend (P = .09). The multivariate model simultaneously included VEGF (relative risk [RR] for death, 8.01; P = .001 for levels less than or equal to 19.5 pg/mL), IL-1Ralpha (RR, 5.12; P = .007 for levels greater than 373 pg/mL), and VEGFR2 (RR, 4.01; P = .04 for levels greater than 8222 pg/mL) as independent factors for survival. Of interest is the association of high levels of VEGF with good prognosis and higher levels of VEGF receptors with poor outcome. These data reflect the complexity by which angiogenic factors may affect the clinical behavior of patients with ALL, and this complexity should be considered in any therapeutic strategy incorporating antiangiogenic agents.
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PMID:Angiogenic factors may have a different prognostic role in adult acute lymphoblastic leukemia. 1612 21

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