Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Markers of inflammation (eg, interleukin-6 [IL-6]), and endothelial perturbation (von Willebrand factor [VWF], circulating endothelial cells [CECs]) are altered in acute coronary syndromes (ACS). We hypothesized that CECs and IL-6 levels during the first 48 hours of ACS would predict 30-day and 1-year major cardiovascular end points (MACE). A total of 156 patients with ACS were included. Blood was drawn on admission (baseline) and 48 hours later for plasma VWF, IL-6 (both enzyme-linked immunosorbent assay [ELISA]), and CECs (CD146 immunomagnetic separation). CEC phenotyping was performed by indirect immunoperoxidase staining. At 30 days, 48 patients had a MACE, a predicted by baseline and 48-hour CECs and IL-6 levels, 48-hour VWF levels, and by the "admission-48 hour change" (Delta) in CECs, VWF, and IL-6 (all P = .002). On multivariate analysis, 48-hour CECs (P < .001) were the strongest predictor of MACE, followed by DeltaIL-6 (P = .01) and DeltaVWF (P = .048); 48-hour CECs were the only predictor of death (P = .007). At 1 year, 65 patients had MACE, predicted by 48-hour CECs and DeltaIL-6 levels (P < .001); age (P = .046) and 48-hour CECs (P < .001) were the only predictors of death. CECs stained 93% positive for endothelial nitric oxide synthase (eNOS) but were less than 1% positive for CD34, CD36, and CD45 and less than 3% for CD31. Like raised VWF, abnormal CECs and IL-6 levels during the first 48 hours of ACS were strongly associated with 30-day MACE. CECs at 48 hours were the only independent predictor of both death and MACE at 30 days and 1 year, indicating the crucial role of endothelial/vascular damage in ACS pathophysiology.
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PMID:Circulating endothelial cells, von Willebrand factor, interleukin-6, and prognosis in patients with acute coronary syndromes. 1537 79

Several reports have shown that the expression of Sca-1 (Ly-6A/E), the most widely used murine hematopoietic stem cell marker, is restricted to blood vessels in several nonhematopoietic tissues. However, there is no information about which components are expressing Sca-1, and what the role of Sca-1 could be. Because we have previously shown that murine liver endothelial cells from the hepatic sinusoid (LSEC) express some HSC markers (i. e., CD34 and c-kit), we hypothesized that these cells could also express Sca-1. In this work, we show that Sca-1 is constitutively expressed in LSEC, as well as in the liver sinusoid lumen. The expression of Sca-1 in LSEC was confirmed at the mRNA and protein level by reverse transcriptase (RT)-PCR, flow cytometry, and immunofluorescence studies. The expression of Sca-1 was enhanced on the surface of LSEC by tumor necrosis factor (TNF). We examined whether Sca-1 ligation on the surface of LSEC regulates some biological response in these cells. Our results show that ligation of Sca-1 by the anti-Ly-6A/E monoclonal antibody (mAb) D7 stimulated the growth of LSEC and the production of interleukin-6 (IL-6) by these cells. To our knowledge, this is the first report that LSEC express Sca-1, which may constitute additional support to the theory of a common progenitor for the hematopoietic and endothelial cells. Our results show a novel role of Sca-1, indicating that it induces activation of LSEC to proliferate and to produce IL-6. These results suggest that Sca-1 may participate in several clinical conditions such as angiogenesis and inflammation.
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PMID:Expression of the hematopoietic stem cell antigen Sca-1 (LY-6A/E) in liver sinusoidal endothelial cells: possible function of Sca-1 in endothelial cells. 1558 10

The myelodysplastic syndromes (MDS) are a group of disorders characterized by dysplastic hemopoiesis and an increased risk of leukemic transformation. The process of angiogenesis has been implicated in the pathogenesis and evolution of MDS. In this study the proliferative activity and extent of angiogenesis was examined in bone marrow samples from 54 patients with MDS in relation to clinicopathologic features. Cellular proliferation and microvascular density (MVD) were examined immunohistochemically, using the monoclonal antibody MIB-1 (Ki-67) and an anti-CD34 monoclonal antibody respectively. Serum concentrations of interleukin-6 (IL-6) were measured by ELISA. The results showed that the MIB-1 Labeling Index (MIB-1 LI), MVD and IL-6 increased significantly with advancing severity of disease. Among the MDS-FAB subtypes, MIB-1 LI, MVD and IL-6 were significantly higher in RAEB-t, RAEB and CMML in comparison to RA and RARS (p < 0.0001 in all cases). Similarly, MIB-1 and MVD were increased in patients with score 3 in comparison to scores 0 and 1 in the IPSS system (p < 0.05). All parameters studied were significantly higher in patients versus controls. We conclude that cellular proliferative activity and angiogenesis are associated with disease progression in MDS patients.
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PMID:Expression of the proliferation-associated nuclear protein MIB-1 and its relationship with microvascular density in bone marrow biopsies of patients with myelodysplastic syndromes. 1560 99

It has been suggested that epigenetic regulation plays an important role in maintaining the stemness and lineage differentiation of hematopoietic stem cells (HSCs), 5-aza-deoxycytidine (aza-D) and Trichostatin A (TSA) being candidate additives for HSC ex vivo expansion. Although they have potent activity to maintain the stemness, they can also cause serious cell death. This study examined the effects of mesenchymal stem cells (MSCs) on the maintenance of CD34+ cells driven by aza-D and TSA in culture with the combined cytokines of thrombopoietin, flt-3 ligand, stem cell factor, interleukin-3, and interleukin-6. In cultures without MSCs, although aza-D and TSA retained the CD34 frequency 4 to 8 times more than in the cytokines alone, a large portion of cells underwent apoptotic cell death. Consequently, CD34+ cell expansion could not be achieved in any condition without MSCs. In cultures with MSCs, the total cell number was higher in aza-D or TSA than in any conditions in the cultures without MSCs. The CD34 frequency was also similar to the level in the cultures in aza-D or TSA without the MSCs. These results suggest that a co-culture of CD34+ cells with the MSCs might not simply deliver the proliferation signals but also stemness and survival signals, and overlap the action of epigenetic regulators.
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PMID:Co-culture of human CD34+ cells with mesenchymal stem cells increases the survival of CD34+ cells against the 5-aza-deoxycytidine- or trichostatin A-induced cell death. 1575 60

Interleukin-6 (IL-6) protects multiple myeloma cells against apoptosis induced by glucocorticoids. Here, we investigated whether inhibition of the IL-6 signaling pathway by the IL-6 receptor superantagonist Sant7 enhances the in vivo antitumor effects of dexamethasone on the IL-6-dependent multiple myeloma cell line INA-6. For this purpose, we used a novel murine model of human multiple myeloma in which IL-6-dependent INA-6 multiple myeloma cells were directly injected into human bone marrow implants in severe combined immunodeficient (SCID) mice (SCID-hu). The effect of in vivo drug treatments on multiple myeloma cell growth was monitored by serial determinations of serum levels of soluble IL-6 receptor (shuIL-6R), which is released by INA-6 cells and served as a marker of tumor growth. In SCID-hu mice engrafted with INA-6 cells, treatment with either Sant7 or dexamethasone alone did not induce significant reduction in serum shuIL-6R levels. In contrast, the combination of Sant7 with dexamethasone resulted in a synergistic reduction in serum shuIL-6R levels after 6 consecutive days of treatment. Gene expression profiling of INA-6 cells showed down-regulation of proliferation/maintenance and cell cycle control genes, as well as up-regulation of apoptotic genes in multiple myeloma cells triggered by Sant7 and dexamethasone combination. In vitro colony assays showed inhibition of myeloid and erythroid colonies from normal human CD34(+) progenitors in response to dexamethasone, whereas Sant7 neither inhibited colony growth nor potentiated the inhibitory effect of dexamethasone. Taken together, these results indicate that inhibition of IL-6 signaling by Sant7 significantly potentiates the therapeutic action of dexamethasone against multiple myeloma cells, providing the preclinical rationale for clinical trials of Sant7 in combination with dexamethasone to improve patient outcome in multiple myeloma.
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PMID:Combination therapy with interleukin-6 receptor superantagonist Sant7 and dexamethasone induces antitumor effects in a novel SCID-hu In vivo model of human multiple myeloma. 1593 Mar 64

The objectives of this study were to explore whether ovarian vascular endothelial growth factor (VEGF) expression in mice can be regulated by IL-6 (interleukin-6), angiotensin II, FSH, and hCG; and to test whether the mouse ovarian VEGF expression can result in angiogenesis. The ICR mice were sacrificed, and their ovaries were recovered. Recovered ovaries were treated with IL-6, angiotensin II, FSH, and hCG separately and incubated for 24 hours in alpha-MEM. Expression of mRNA and protein of VEGF were assessed by RT-PCR and immunohistochemistry. The resulting angiogenesis was evaluated through immunohistochemical analysis for CD34. Treatment of mice ovaries with IL-6, FSH, and hCG resulted in a significant increase of VEGF mRNA, and IL-6 was the most potent inducer of VEGF. IL-6 and FSH resulted in increased neovascularization in the follicular phase of mouse ovaries. In contrast, angiotensin II could not increase VEGF expression or neovascularization. We documented an in vitro increase in VEGF expression by IL-6, FSH, and hCG; and reaffirmed that the proliferative response of murine ovarian endothelial cells paralleled an increase of VEGF expression.
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PMID:The regulators of VEGF expression in mouse ovaries. 1625 67

The aim of this study was to investigate the growth, immunophenotype and interleukin-6 (IL-6) level of bone marrow stromal cells (BMSC) in patients with acute leukemia (AL) and multiple myeloma (MM). BMSC was cultured by wall-adhesion method and the growth of BMSC was observed. The immunophenotype and cell cycle of BMSC were detected by flow cytometry. The level of interleukin 6 (IL-6) in BMSC culture system was detected by ELISA. The results showed that the primary (17.3 +/- 7.8 days) and continuous (10.3 +/- 3.5 days) growth cycle of BMSC in patients with AL were significantly shorter than those in patients with MM (26.5 +/- 6.3 and 16.5 +/- 4.1 days respectively), and shorter than those in normal controls (25.8 +/- 6.3 and 17.5 +/- 2.4 days) respectively. Similarly, S + G2% (17.4 +/- 3.6%) of BMSC in patients with AL was significantly higher than those in patients with MM (8.5 +/- 2.2%) and in normal controls (8.9 +/- 2.3%). All of the three groups showed positive antigen expressions with CD29 and CD44 were 100%, while CD138, CD34, CD54, CD56 positive were not expressed and CD106 was partially expressed positive. The supernatant IL-6 level of BMSC system in MM patients (1288.5 +/- 736.7 pg/ml) was significantly higher than those in AL patients (859.3 +/- 203.1 pg/ml) and normal controls (850.9 +/- 129.5 pg/ml). It is concluded that the growth, S + G2% of cell cycle and IL-6 level of BMSC in patients with MM, AL and normal control are significantly different, whereas the antigen expressions are similar.
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PMID:[Growth, immunophenotype and interleukin-6 level of bone marrow stromal cells in patients with multiple myeloma and acute leukemia]. 1692 3

In animals, the bone marrow (BM) is a source of liver-repopulating cells with therapeutic potential in case of tissue damage. However, the early response of human BM-derived stem cells (SC) to liver injury is still unknown. Here, we studied 24 patients undergoing orthotopic liver transplantation (OLT) for end-stage liver disease or hepatocellularcarcinoma, and 13 patients submitted to liver resection. The concentration of circulating BM-derived SC was determined by phenotypic analysis and clonogenic assays. Moreover, we assessed the serum level of inflammatory and tissue-specific cytokines. Reverse transcriptase-polymerase chain reaction and fluorescence-in situ hybridization were also used to characterize mobilized SC. At baseline, patients showed a significant lower concentration of circulating CD133(+), CD34(+) SC and clonogenic progenitors (colony-forming unit cells) than healthy controls. However, the time-course evaluation of peripheral blood cells after OLT demonstrated the significant early mobilization of multiple subsets of hematopoietic and endothelial stem/progenitor cells. Cytogenetic and molecular analyses of CD34(+) cells showed the host origin of mobilized SC and the expression of transcripts for GATA-4, cytokeratin 19, and alpha-fetoprotein hepatocyte markers. In contrast with OLT, only total circulating CD34(+) cells significantly increased after liver resection. Mobilization of BM cells after OLT or liver surgery was associated with increased serum levels of granulocyte-colony stimulating factor, interleukin-6, stem cell factor, hepatocyte growth factor, and vascular endothelial growth factor. In summary, we demonstrate that tissue damage after OLT and liver resection induces increased serum levels of multiple cytokines but only ischemia/reperfusion injury associated with OLT results in the remarkable mobilization of BM stem/progenitor cells.
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PMID:Mobilization of bone marrow-derived hematopoietic and endothelial stem cells after orthotopic liver transplantation and liver resection. 1693 69

This study was designed to investigate the regulatory role of soluble interleukin-6 receptor (sIL-6R) and interleukin-6 (IL-6) fusion protein (Hyper-IL-6) in the differentiation of human myeloid and erythroid progenitors by a serum-free liquid suspension culture system, using the human cord blood-derived CD34(+)CD38(-) cells as a target. We found that Hyper-IL-6 promoted the generation of CD15(+) granulocytic and CD14(+) monocytic cells and suppressed that of CD14(-)CD1a(+) dendritic cells from CD36(-)CD15(-)CD14(-)CD1a(-)IL-6R(+) myeloid progenitors. Conversely, CD34(+)CD38(-) cell-derived early erythroid progenitors were negative for IL-6R expression. Hyper-IL-6 potentiated the generation of CD36(+)glycophorinA(high) mature erythroid cells from the IL-6R(-) early erythroid progenitors. Our results indicate that Hyper-IL-6 augments the generation of CD15(+) granulocytic, CD14(+) monocytic and CD36(+)glycophorinA(high) cell and suppresses that of CD14(-)CD1a(+) dendritic cells.
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PMID:The regulatory role of Hyper-IL-6 in the differentiation of myeloid and erythroid progenitors derived from human cord blood. 1693 90

Within the bone marrow (BM), hematopoietic progenitor cells (HPCs) are localized in poorly oxygenated niches where they interact with the surrounding osteoblasts (OBs) through VLA4/VCAM-1 engagement, and are exposed to interleukin-6 (IL-6), stem cell factor (SCF), and chemokines such as CXCL12 (OB factors). Umbilical cord (UC) is more highly oxygenated that the BM microenvironment. When UC-HPCs are exposed to the 2% to 3% O(2) concentration found in the bone endosteum, their survival is significantly decreased. However, engagement of VLA-4 integrins on UCB-derived CD34(+) cells reduced cell death in 2% to 3% O(2) conditions, which was associated with an increase in phospho-Ser473 AKT and an increase in phospho-Ser9 GSK3b. Consistent with the role of GSK3b in destabilizing beta-catenin, there was more cytoplasmic beta-catenin in UC-HPCs exposed to 2% to 3% O(2) on fibronectin, compared with suspension culture. UC-HPCs cultured at 2% to 3% O(2) with OB factors showed an increase in nuclear beta-catenin and persistence of a small pool of CD34(+)38(-) HPCs. CFU assays followed by surface phenotyping of the plated colonies showed improved maintenance of mixed lineage colonies with both erythroid and megakaryocytic precursors. These studies provide a biologic perspective for how UC-derived HPCs adapt to the bone endosteum, which is low in oxygen and densely populated by osteoblasts.
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PMID:Biology of umbilical cord blood progenitors in bone marrow niches. 1737 47


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