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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies were carried out on some biological activities of Helicobacter pylori porins in vitro. We extracted and purified a porin with an apparent molecular mass of 30 kDa. Human polymorphonuclear leukocytes preincubated with H. pylori porins showed a decrease of chemotaxis, of adherence to nylon wool, and of chemiluminescence. Used as chemotaxins in place of zymosan-activated serum or as chemotaxinogens in place of zymosan, the porins induced polymorphonuclear leukocyte migration. Human monocytes and lymphocytes cultivated in the presence of H. pylori porins released cytokines. Release of the various cytokines studied was obtained with differentiated kinetics and at various porin concentrations. Starting only 3 h after culture, tumor necrosis factor alpha is released quickly, reaching a peak at 18 h, at a porin concentration of 1 microgram/ml/10(6) cells. Interleukin-6 (IL-6) appears later, with a peak at 10 micrograms/ml/10(6) cells, while IL-8 is released after 6 h of culture, with a peak at 24 h, at a porin concentration of 10 micrograms/ml/10(6) cells, while IL-8 is released after 6 h of culture, with a peak at 24 h, at a porin concentration of 10 micrograms/ml/10(6) cells. Lymphocytes stimulated by H. pylori porins release gamma interferon after 18 h of culture at higher concentrations of porins (20 micrograms/ml/10(6) cells). Granulocyte macrophage colony-stimulating factor is released from 6 to 48 h at a concentration of 1 microgram/ml/10(6) cells, while both IL-3 and IL-4 are released after 18 h of culture at different porin concentrations (0.1 and 1 microgram/ml/10(6) cells, respectively). Our results lead us to think that during H. pylori infection, surface components, porins in particular, are able to induce a series of chain reactions ranging from the inflammatory to the immunological responses.
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PMID:Immunobiological activities of Helicobacter pylori porins. 813 46

In order to induce acquired cellular resistance (ACR) to facultative intracellular bacterial pathogens, infection with live organisms is required. It is possible that different cytokine responses to live bacteria or their extracted antigens could account for their different abilities to induce ACR. Therefore, mice were infected with live attenuated Brucella abortus vaccine strain 19, and their ability to produce cytokines, both in vivo and in vitro, was investigated over 12 weeks of infection. This was compared with the response to injection of soluble brucella proteins (SBP). During infection, serum levels of interleukin-6 (IL-6) were markedly increased over a period of 4 weeks during the peak of infection. SBP plus adjuvant induced a transient increase in serum IL-6. IL-1 and tumour necrosis factor-alpha (TNF-alpha) remained undetectable in both instances. Spleen cells taken at intervals after infection and cultured with brucella antigens produced high titres of IL-6, IL-1 and TNF-alpha. Immunization with SBP was less efficient than live infection at inducing these cytokines. Of the characteristically T-cell-derived lymphokines, interferon-gamma (IFN-gamma) production rose 2 weeks after infection, peaking at 6 weeks, while IL-2 was not detected until 6 weeks post-infection. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was produced in substantial amounts, but IL-3 production was minimal. In contrast, spleen cells from mice immunized with SBP produced IL-2 but failed to produce IFN-gamma. The implications of these results for the induction of ACR are discussed.
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PMID:Cytokine production in the murine response to brucella infection or immunization with antigenic extracts. 828 19

The purpose of these studies was to examine the effects of in vivo and in vitro recombinant IL-3 treatment on alveolar macrophage and monocyte activities associated with antitumor and antimicrobial properties. Alveolar macrophages and blood monocytes from 6 patients receiving IL-3 (125-500 micrograms/m2/day) subcutaneously were isolated before therapy and at various times during the 15 days of therapy. Results indicated that tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1), and interleukin-6 (IL-6) secretion were enhanced from monocytes of all patients and from alveolar macrophages of patients receiving 500 micrograms/m2/day IL-3. Constitutive cytokine gene expression was present before therapy, but further enhancement was not detectable during therapy, suggesting a rapid time course of cytokine gene transcription and translation. Serum neopterin levels were elevated 2-5 fold in all patient compatible with the presence of augmented monocyte/macrophage activity. Peak levels of neopterin did not coincide with peak levels of cytokine secretion. In vitro studies of IL-3-treated normal alveolar macrophage and monocyte population demonstrated that IL-3 significantly augmented TNF and IL-6 secretion in monocytes, but not in alveolar macrophages. These differences in alveolar macrophage cytokine secretion observed after in vivo and in vitro IL-3 treatment may reflect the involvement of other cell populations in IL-3 modulation of alveolar macrophages in vivo. Monocytes, in contrast were comparably activated by IL-3 whether presented in vitro or in vivo.
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PMID:Immunomodulatory effects of recombinant interleukin-3 treatment on human alveolar macrophages and monocytes. 839 69

Embryonic hematopoiesis is initiated in part in the blood islands of the yolk sac. Previous confocal microscopic analysis has shown that the CD34 antigen, a mucin-like cell surface glycoprotein that is expressed by hematopoietic progenitors and all endothelial cells of the adult and embryo, is also found on a subset of luminal hematopoietic-like cells in the yolk sac blood islands as well as on the vascular endothelium lining these early hematopoietic locations. We show here that, as in all other hematopoietic sites thus far examined, immunoaffinity-purified CD34+ nonadherent cells from murine yolk sacs contain the vast majority of erythroid and myeloid progenitor cell colony forming activity. To examine the developmental interactions between these CD34+ hematopoietic progenitor cells of the yolk sac and the CD34+ yolk sac endothelium, we have immunaffinity-purified adherent endothelial cells from day 10.5 yolk sacs using CD34 antiserum and produced cell lines by transformation with a retrovirus expressing the polyoma middle T antigen. Analysis of these cell lines for CD34, von Willebrand's factor, FLK 1 and FLT 1 expression, and capillary growth in Matrigel indicates that they appear to be endothelial cells, consistent with their original phenotype in vivo. Coculture of yolk sac CD34+ hematopoietic cells on these endothelial cell lines results in up to a 60-fold increase in total hematopoietic cell number after approximately 8 days. Analysis of these expanded hematopoietic cells showed that the majority were of the monocyte/macrophage lineage. In addition, examination of the cultures showed the rapid formation of numerous cobblestone areas, a previously described morphologic entity thought to be representative of early pluripotential stem cells. Scrutiny of the ability of these endothelial cell lines to expand committed progenitor cells showed up to a sixfold increase in erythroid and myeloid colony-forming cells after 3 to 6 days in culture, consistent with the notion that these embryonic endothelial cells mediate the expansion of these precursor cells. Polymerase chain reaction analyses showed that most of the cell lines produce FLK-2/FLT-3 ligand, stem cell factor, macrophage colony-stimulating factor, leukemia-inhibitory factor, and interleukin-6 (IL-6), whereas there is a generally low or not measurable production of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, IL-1, IL-3, transforming growth factor beta-1, erythropoietin, or thrombopoietin. The output of mature hematopoietic cells from these cocultures can be modified to include an erythroid population by the addition of exogenous erythropoietin. These data suggest that endothelial cell lines derived form the yolk sac provide an appropriate hematopoietic environment for the expansion and differentiation of yolk sac progenitor cells into at least the myeloid and erythroid lineages.
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PMID:CD34+ endothelial cell lines derived from murine yolk sac induce the proliferation and differentiation of yolk sac CD34+ hematopoietic progenitors. 854 34

We have reported that serum granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6) levels rise in patients with chemotherapy-induced myelosuppression. The aim of the present study was to determine whether other cytokines that function at different hematopoietic stages also fluctuate during chemotherapy-induced myelosuppression and whether the extent of cytokine level fluctuations correlate with myelosuppression severity. Fifteen patients participated in the study. Serum levels of stem cell factor (SCF), interleukin (IL)-1 alpha, IL-6, IL-3, granulocyte-macrophage CSF (GM-CSF) and G-CSF were analyzed before chemotherapy and during the myelosuppressive stage and correlations between cytokine levels and myelosuppression severity were examined. The results showed that both serum G-CSF and IL-6 levels rose in patients with chemotherapy-induced myelosuppression. The prechemotherapy serum G-CSF and IL-6 levels correlated well with their respective elevated levels during the myelosuppressive stage. The myelosuppression severity also correlated well with the extent of serum G-CSF level elevation. The serum IL-6 and G-CSF levels during the myelosuppressive stage correlated significantly. Serum SCF levels did not fluctuate significantly during myelosuppression, and IL-1, IL-3 and GM-CSF were rarely detected in serum even after chemotherapy. In the present study, the roles of IL-1 alpha, SCF, IL-3 and GM-CSF chemotherapy-induced myelosuppression were not clear.
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PMID:Serum cytokine level fluctuations in chemotherapy-induced myelosuppression. 855 62

We investigated the effects of stem cell factor (SCF) on the growth of blast clonogenic cells from 27 patients with acute myeloblastic leukemia (AML) and 3 patients with chronic myelocytic leukemia in myeloid crisis. SCF alone showed a significant stimulatory activity in 15 of 30 patients (50%). A marked reduction in the number of blast cell colonies supported by SCF alone was noted by the addition of neutralizing antibody (Ab) against granulocyte-macrophage colony-stimulating factor (GM-CSF). Ab against interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) also moderately reduced the number of colonies, whereas Ab against granulocyte CSF (G-CSF) failed to do so. All four Ab together completely abolished the growth in 5 of 6 patients tested. c-kit antisense oligonucleotides reduced the colony formation supported by IL-3 or G-CSF or, in the absence of growth factor, in only 2 of 10 patients tested. SCF caused stimulation by acting synergistically with G-CSF, GM-CSF, IL-3, IL-6, IL-9, IL-11, and IL-12 in 20 of 27 (74%), 17 of 27 (63%), 14 of 28 (50%), 9 of 28 (32%), 1 of 15 (7%), 3 of 28 (11%), and 2 of 15 (13%) patients, respectively. Thus, SCF alone or in combination with some other factor stimulated the growth in 27 of 30 (90%) patients. Of 3 nonresponders, 2 were AML, M3 at presentation. G-CSF at the optimal concentration increased the sensitivity of blasts to SCF. Taken together, SCF acting in combination with other factors, but not alone, stimulates the growth of blast clonogenic cells. GM-CSF, IL-6, and TNF-alpha may be produced endogenously, whereas G-CSF and SCF may be supplied exogenously. Autocrine regulation of the growth of blasts seems to increase the responsiveness of the cells to any of these factors, allowing them to achieve a highly active growth state.
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PMID:Roles of stem cell factor in the in vitro growth of blast clonogenic cells from patients with acute myeloblastic leukemia. 856 3

Oncostatin M (OSM) is a member of the interleukin-6 (IL6)-related cytokine subfamily that includes IL6, IL11, leukemia inhibitory factor (LIF), ciliary neurotrophic factor and cardiotrophin-1. While human OSM has been characterized and the bovine OSM gene was recently cloned, the murine counterpart had not been identified. Here we describe molecular cloning of murine OSM as an immediate early gene induced by a subset of cytokines including IL2, IL3 and erythropoietin (EPO) in myeloid and lymphoid cell lines. The induction kinetics of OSM are rapid and transient, reaching a maximal level within 30-60 min and decreasing thereafter. Induction of OSM depends on the signals generated by the membrane-proximal region of the EPO receptor as well as that of the beta chain of the IL3/GM-CSF receptor, which activate JAK2 and STAT5. About 100 bases upstream of the transcription initiation site of the OSM gene contains a possible STAT5 binding site which is essential for IL2, IL3 and EPO-dependent promoter activity of the OSM gene. Expression of STAT5 and the EPO receptor in COS cells conferred EPO-dependent activation of the OSM promoter. Moreover, the mutant IL2 receptor lacking the ability to activate STAT5 induced c-myc but failed to induce OSM. Thus OSM is one of the common targets of a subset of cytokines that activate STAT5. The murine OSM gene is located near to the LIF gene, expressed at high levels in bone marrow and possesses similar biological activity to human OSM. Identification of murine OSM as a cytokine-inducible immediate early gene provides a new insight into the physiological function of this unique cytokine.
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PMID:Mouse oncostatin M: an immediate early gene induced by multiple cytokines through the JAK-STAT5 pathway. 860 75

In this study the distribution and quantitation of the flt3/flk-2 receptor was examined on bone marrow cells and defined haemopoietic subpopulations. Undifferentiated cells expressed the greatest numbers of flt3/flk-2 receptors: 19% of primitive lin-kit+sca-1+ bone marrow cells and 16% of fetal liver lin-aa4.1+ cells exhibited over 15 000 receptors per cell as determined by binding of the radiolabeled cognate ligand (flt3/flk-2 ligand, FL). Moderate binding was demonstrated on early B lymphocyte subsets (4400 receptors per cell) and very low levels were detected on monocytes. Binding was not detected on promyelocytes, myelocytes, promonocytes, metamyelocytes, polymorphonuclear cells, eosinophils or nucleated erythroid cells. FL enhanced the survival of primitive lin kit+sca-1+ cells with an efficacy s with an efficacy equivalent to stem cell factor (SCF). FL stimulated predominantly blast and granulocyte-macrophage colony formation in cultures of bone marrow cells by both direct and indirect mechanisms. Marked synergistic effects of FL with combinations of colony stimulating factors (CSFs) or interleukin-6 occurred in the proliferation of primitive lin-kit+sca-1+ cells, but not lin-kit+sca-1- progenitor cells. Surprisingly, recloning experiments revealed that FL plus IL-3 increased the generation of progenitor cells by lin-kit a-1- cells compared with SCF plus IL-3. Thus FL functions as a factor with both direct and indirect stimulatory activities directed to the expansion, maintenance of clonogenic potential, and possibly limited self-renewal, of early haemopoietic cells.
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PMID:The flt3/flk-2 ligand: receptor distribution and action on murine haemopoietic cell survival and proliferation. 860 17

Recombinant thrombopoietin has been reported to stimulate megakaryocytopoiesis and thrombopoiesis and it may be quite useful to treat patients with low platelet counts after chemotherapy. As little is known regarding the possible activation of platelets by thrombopoietin, we examined the effects of thrombopoietin on platelet aggregation induced by shear stress and various agonists in native plasma. Using hirudin as an anticoagulant, thrombopoietin (1 to 100 ng/mL) enhanced platelet aggregation induced by 2 micromol/L adenosine-diphosphate (ADP) in a dose dependent fashion. The enhancement was not affected by treatment of platelets with 1 mmol/L aspirin plus SQ-29548 (a thromboxane antagonist, 1 micromol/L) but was inhibited by a soluble form of the thrombopoietin receptor, suggesting that the enhancement was mediated by the specific receptors and does not require thromboxane production. Epinephrine (1 micromol/L), which does not induce platelet aggregation in hirudin platelet rich plasma (PRP), did so in the presence of thrombopoietin (10 ng/mL). Thrombopoietin (10 ng/mL) also enhanced or primed platelet aggregation induced by collagen (0.5 micron.mL),. thrombin, serotonin, and vasopressin. Thrombopoietin does not induce any rise in cytosolic ionized calcium concentration nor activation of protein kinase C, as estimated by phosphorylation of preckstrin, indicating that the priming effects of thrombopoietin does not require those processes. The ADP- or thrombin-induced rise in cytosolic ionized calcium concentration was not enhanced by thrombopoietin (100 ng/mL). Further, shear (ca. 90 dyn/cm2)-induced platelet aggregation was also potentiated by thrombopoietin. The priming effect on epinephrine-induced platelet aggregation in hirudin PRP was unique to thrombopoietin, with no effects seen using interleukin-6 (IL-6), IL-11, IL-3, erythropoietin, granulocyte-colony stimulating factor, granulocyte macrophage-colony stimulating factor, or c-kit ligand. These data indicate that monitoring of platelet functions may be necessary in the clinical trials of thrombopoietin.
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PMID:Thrombopoietin primes human platelet aggregation induced by shear stress and by multiple agonists. 863 35

We demonstrated bundle formation of microtubules both in the cytoplasmic processes and in the cytoplasm near the nucleus of cultured megakaryocytes by means of electron and immunofluorescent microscopy. To determine whether this bundle formation was related to megakaryocyte maturation, we studied the effects of recombinant human interleukin-6 (rhIL-6) in vitro and in vivo on this event. About 75% of the megakaryocytes in the bone marrow had no fibrous microtubule structures in the cytoplasm (type I), and about 25% had bundles of microtubules (type II). The formation of these bundles was promoted by rhIL-6 both in vitro and in vivo. Considerably more megakaryocytes cultured with recombinant murine (rm) IL-3 and rhIL-6 became type II than those cultured with rmIL-3 alone. Megakaryocytes from mice given rhIL-6 (10 microg/animal/d) subcutaneously also began to form bundles in proportion to an increase in platelet counts. After the administration of rhIL-6, about half of the megakaryocytes contained microtubule bundles in their cytoplasm. These results indicate that microtubule-bundle formation is one maturational event in megakaryocyte development and that rhIL-6 could accelerate this event.
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PMID:A novel aspect of the maturational step of megakaryocytes in thrombopoiesis: bundle formation of microtubules in megakaryocytes. 864 55


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