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

Expression of the interleukin-6 (IL-6) receptor on B cells and plasma cells in the bone marrow (n = 18) and peripheral blood (n = 32) of patients with multiple myeloma and the relative saturation of these receptors with endogenous IL-6 has been determined by dual-labelled flow cytometric analyses. B cells were identified using an anti-CD19 monoclonal antibody and plasma cells were identified by gating on cells with high fluorescent staining with anti-CD38. With the exception of one patient, very few bone marrow plasma cells expressed the IL-6 receptor (IL-6R) (mean = 2%). This was in contrast to cells from the U-266 plasma cell line, 90% of which had IL-6R. IL-6R expression was lower on bone marrow B cells (mean = 11%) than on peripheral blood B cells (mean = 69%). Studies using either monoclonal or polyclonal anti-human IL-6 to detect endogenous receptor-bound IL-6 found that the IL-6R on bone marrow B cells and plasma cells from patients with multiple myeloma were not saturated with endogenous IL-6 and the presence of receptor-bound IL-6 tended to be associated with stable disease. Thus dysregulated IL-6R expression was not evident on the B cells and plasma cells of patients with multiple myeloma and the increased IL-6R expression on the U-266 plasma cell line was not found on patients' cells.
Leukemia 1993 Feb
PMID:Interleukin-6 receptor expression and saturation on the bone marrow cells of patients with multiple myeloma. 842 76

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.
Leukemia 1995 Dec
PMID:The flt3/flk-2 ligand: receptor distribution and action on murine haemopoietic cell survival and proliferation. 860 17

Stromal cell lines were established by irradiating adherent layers of bone marrow and spleen cells in Dexter-type long-term culture with X-rays. Some of these cell lines support myelopoiesis and/or B lymphopoiesis in vitro. Furthermore, the characteristics of these stromal cell lines were studied. Cytokine activity was detected in the conditioned media from all hematopoietic-supportive and non-supportive stromal cells. Quantitative reverse transcriptase-polymerase chain reaction analysis revealed that the mRNAs of macrophage colony-stimulating factor and stem cell factor, but not that of Interleukin-3, were detectable in all the hematopoietic-supportive and non-supportive stromal cell lines. The transcripts of granulocyte colony-stimulating factor, interleukin-6, interleukin-7, and leukemia inhibitory factor were expressed in a wide variety of cell lines. Most stromal cell lines synthesized mRNA of c-mpl, the ligand of which stimulates megakaryopoiesis and thrombopoiesis. These observations indicate that the pattern of mRNA expression of cytokines is not correlated with the hematopoietic-supportive ability of stromal cell lines. There was a significant difference in the efficiency of adhesion of lineage marker-negative bone marrow cells to fibroblasts and stromal cell lines. This appears to be correlated with the hematopoietic-supportive ability of the stromal cell lines.
Leukemia 1996 May
PMID:Characterization of murine stromal cell clones established from bone marrow and spleen. 865 75

Interleukin-10 (IL-10), like IL-4, is known to inhibit cytokine expression in activated human monocytes. We showed that both IL-10 and IL-4 inhibit LPS-induced IL-6 mRNA and protein expression by inhibiting the transcription rate of the IL-6 gene. The strong inhibition of the IL-6 transcription rate prompted us to study the effect of IL-10 and IL-4 on the expression of transcription factors. We questioned whether or not IL-10 and IL-4 affected the expression of transcription factors that are known to be involved in the control of the IL-6 transcription rate, namely activator protein-1 (AP-1), nuclear factor IL-6 (NF-IL6), and nuclear factor kappa B (NF-kappaB). In electrophoretic mobility shift assays (EMSAs) we showed that IL-10 and IL-4 inhibited LPS-induced AP-1 binding activity. The inhibiting effect of IL-4 was slightly more pronounced than that of IL-10. Downregulation of LPS-induced AP-1 was accompanied, and thus possibly explained, by a reduced expression at mRNA level of the two major components of the AP-1 complex, namely c-fos and c-jun as determined by Northern experiments. Binding activity of NF-IL6 was also strongly inhibited by IL-4 whereas IL-10 showed no effect. NF-IL6 mRNA levels were not affected by IL-10 or IL-4, suggesting that IL-4 affects binding activity of preexisting NF-IL6. Neither IL-10 nor IL-4 inhibited LPS-induced NF-kappa B binding activity. In agreement with this finding, Northern experiments where p65 and p105 mRNA levels were determined, demonstrated that expression of these components of the NF-kappa B transcription factor were not affected by IL-10 or IL-4. Furthermore, neither IL-10 nor IL-4 showed any effect on I-kappa B mRNA expression as determined by Northern experiments. Thus, IL-10 and IL-4 similarly affect IL-6 expression. However, for IL-4 this was accompanied with a reduction of AP-1 and NF-IL6 binding activity whereas IL-10 only inhibited AP-1 binding activity.
Leukemia 1996 Aug
PMID:Effects of IL-10 and IL-4 on LPS-induced transcription factors (AP-1, NF-IL6 and NF-kappa B) which are involved in IL-6 regulation. 870 36

The expression of transcripts of cytokines of the interleukin-6 (IL-6) family has been examined in human breast tumors, breast cancer cell lines, and adipose stromal cells, by means of reverse transcription polymerase chain reaction amplification. Of the six breast tumor samples examined, all expressed transcripts encoding IL-6 and Leukemia Inhibitory Factor (LIF). Four of the samples also expressed transcripts for oncostatin M (OSM) and IL-11, and three expressed the IL-6 receptor. Adipose stromal cells expressed IL-6, IL-11 and LIF, but not the IL-6 receptor, consistent with previous conclusions that IL-6 activity in these cells required addition of IL-6 soluble receptor. In the case of T47D cells, expression of IL-11 protein was confirmed by immunotitration. Moreover, in these cells, expression of IL-11 transcripts was induced 3-fold by addition of estradiol to the culture medium. These results add credence to our previous proposal that breast cancer development is regulated in part by local autocrine and paracrine mechanisms via epithelial/mesenchymal interactions, in which estrogen produced by stromal cells surrounding the tumor acts to stimulate the production of growth factors and cytokines by the tumor cells. Some of these may act to stimulate further the growth and development of the tumor, while these or other factors may act on the surrounding mesenchymal cells in a paracrine fashion to stimulate aromatase expression in the presence of glucocorticoids. Thus, a positive feedback loop is established which leads to the development and growth of the tumor.
 ...
PMID:Expression of transcripts of interleukin-6 and related cytokines by human breast tumors, breast cancer cells, and adipose stromal cells. 873 8

Serum levels of cytokines and in vitro cytokine production by lymph node mononuclear cells (LNMC) were studied in four patients with angio-immunoblastic lymphadenopathy with dysproteinemia (AILD) or AILD-type T cell lymphoma. An increased level of serum interleukin-6 (IL-6) was detected on initial diagnosis in both of two patients examined. Spontaneous production of IL-6 by LNMC was detected in all four patients studied. Immunosuppressive therapy with cyclosporin A (CsA) was attempted in a 68-year-old man, who was refractory to intensive combination chemotherapy. The increased level of IL-6 in this patient decreased to normal within 3 weeks of CsA administration and the patient became symptom-free. One and a half months later, the IL-6 level gradually increased along with clinical exacerbation. We also measured serum levels of IL-1 alpha, IL-2, IL-4, IFN-alpha, gamma and TNF-alpha in parallel with IL-6, but these factors were only sporadically detected. IL-6 production by LNMC was stimulated by IL-2 but inhibited by CsA. These observations suggest that IL-6 is one of the important cytokines to be involved in the pathophysiology of AILD and CsA is a useful reagent for relieving symptoms.
Leukemia 1996 Sep
PMID:Increased levels of interleukin-6 (IL-6) in serum and spontaneous in vitro production of IL-6 by lymph node mononuclear cells of patients with angio-immunoblastic lymphadenopathy with dysproteinemia (AILD), and clinical effectiveness of cyclosporin A. 875 70

We studied the applicability of interleukin-6 Pseudomonas exotoxin fusion protein (IL-6PE4E) for treatment of acute myelocytic leukemia (AML). Leukemic cells from five out of 10 AML patients studied expressed IL-6 receptor (IL-6R) and proliferation in vitro was inhibited in four of these cases. The potential of this approach in vivo was tested in a pre-clinical model for AML; the Brown Norway acute myelocytic leukemia (BNML). To obtain IL-6R expression levels on BNML cells comparable to the numbers expressed on human AML, human IL-6R gene transfectants of the BNML sub-line LT12 (LT12/IL-6R) were generated. IL-6PE4E is cytotoxic in vitro to LT12/IL-6R expressing 1400 high affinity IL-6R per cell with 50% inhibition of DNA synthesis at 1 ng/ml. In vivo treatment of leukemic rats carrying LT12/IL-6R leukemia indicated that the maximal tolerated dose of IL-6PE4E was 275 +/- 25 microg/kg/day, when continuously administered for 7 days and resulted in a 90% reduction in leukemic cell load. At this dose level of IL-6PE4E no reduction of normal hemopoietic progenitors was seen in non-leukemic rats. At higher dose levels (350-1050 microg/kg/day) severe systemic toxicity was encountered. On the basis of these pre-clinical studies the feasibility of growth factor-toxins for selective in vivo targeting to AML cells is evaluated.
Leukemia 1996 Nov
PMID:Treatment of acute myelocytic leukemia with interleukin-6 Pseudomonas exotoxin fusion protein in a rat leukemia model. 889 84

Oncostatin M (OSM) is a member of the interleukin-6/leukemia inhibitory factor (LIF) family cytokines. While human OSM (hOSM) has been characterized, the murine counterpart had not been isolated. We cloned a murine OSM (mOSM) cDNA as a gene that is induced in hematopoietic cells by a subset of cytokines including IL-3, GM-CSF and Epo. Identity of mOSM was based on overall homology to hOSM and chromosomal gene localization. Human OSM is known to exhibit biological activities similar to LIF, because they share the same functional receptor composed of the LIF receptor and gp130. As compared to hOSM, however, a 1000-fold higher concentrations of mOSM was required to stimulate proliferation of LIF-dependent murine DA1a cells, differentiation of M1 macrophage cells, and inhibition of ES cell differentiation. On the other hand, mOSM inhibited growth of NIH3T3 cells at a 1000-fold lower concentration than that of hOSM. These results indicate that mOSM functions through a receptor which is distinct from that of the LIF receptor. Studies on the physiological role of OSM is underway.
Leukemia 1997 Apr
PMID:Cloning and biological activity of murine oncostatin M. 920 21

We have detected expression of interleukin-6 receptors (IL-6R) by primary leukemic cells from three of six patients with t(4;11)+ ALL. Scatchard analysis revealed from 960 to 2100 high-affinity IL-6R/cell on these cells (median, 1560; mean, 1540). All three IL-6R+ cases also expressed CD33, which was not expressed on IL-6R-negative cases. To determine if these receptors could serve as a target for a recombinant ligand-toxin, we examined the sensitivity of primary IL-6R+ ALL cells to a recombinant IL6-Pseudomonas exotoxin (IL6-PE4E) fusion protein, in which the toxicity and specificity of the chimeric toxin was enhanced by substitution of four glutamine residues for naturally occurring amino acids in PE domain I. Primary cells from IL-6R+ cases were sensitive to IL6-PE4E in a 48-h cytotoxicity assay, with ID50 values (concentrations causing 50% decrease in viability) ranging from 23 ng/ml to 92 ng/ml (median, 61; mean, 58). Furthermore, incubation of these cells with 10(3) ng/ml IL6-toxin for 24 h prevented their subsequent engraftment in SCID mice. Thus, IL6-PE4E may be useful for ex vivo purging of IL-6R+ leukemic cells in an autologous bone marrow transplantation setting and possibly for therapy of residual, chemotherapy-resistant disease.
Leukemia 1997 Oct
PMID:Expression of interleukin-6 receptors by pediatric acute lymphoblastic leukemia cells with the t(4;11) translocation: a possible target for therapy with recombinant IL6-Pseudomonas exotoxin. 932 1

Agnogenic myeloid metaplasia (AMM) is a disease characterized by bone marrow megakaryocyte hyperplasia and clusters of megakaryocytes, in which many of the megakaryocytes are atypical. In order to elucidate the mechanisms of megakaryocytosis, ELISA assays of blood levels of thrombopoietin (TPO), interleukin-6 (IL-6) and interleukin-11 (IL-11) were done in 45 patients with AMM and compared with normal volunteer controls. Higher blood TPO levels were found in AMM than in controls (P < 0.0001), and blood TPO levels were correlated with the degree of marrow fibrosis (P = 0.0078). Blood levels of IL-6 were also significantly higher in AMM, when compared with controls (P < 0.0001). However, no correlation was found between blood IL-6 levels and degree of marrow fibrosis. No correlation was found between either TPO or IL-6 and the number of blood platelet counts, the number of marrow megakaryocytes, WBC counts, or the degree of splenomegaly. Blood IL-11 levels were undetectable in most patients and no significant difference was found in AMM as compared to controls. The present study demonstrated that, while in idiopathic thrombocytopenic purpura (ITP) or aplastic anemia, blood TPO levels are relatively correlated with the numbers of platelet and/or megakaryocyte mass, blood TPO levels do not correlate with blood platelet counts, or marrow megakaryocyte mass in AMM. Therefore, in AMM, other mechanisms such as the number of TPO receptors on platelets or megakaryocytes, c-MPL receptor abnormalities, abnormal production of TPO mRNA and so on, will have to be studied. Furthermore, TPO may play a significant role in the pathogenesis of marrow fibrosis; IL-6 may be a factor in the development of marrow megakaryocytosis but its elevated blood levels may represent a secondary immune phenomenon; and IL-11 probably does not play a significant role in causing marrow megakaryocytosis in this disease.
Leukemia 1997 Nov
PMID:Blood thrombopoietin, IL-6 and IL-11 levels in patients with agnogenic myeloid metaplasia. 936 14


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