Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant interleukin 1 alpha (rIL-1 alpha) augmented proliferation of freshly isolated myeloma cells as well as B-cell stimulatory factor 2 (BSF-2)/interleukin-6 (IL-6). Recombinant IL-1 alpha-induced proliferation was partially inhibited by anti-IL-6 antibody. In the culture supernatants of rIL-1 alpha-stimulated myeloma cells, IL-6 activities, which were measured by using an IL-6-dependent murine hybridoma clone, MH60.BSF2, were increased, when compared with those in the culture supernatants of nonstimulated myeloma cells. Furthermore, IL-6 messenger RNA (mRNA) expression was also augmented in IL-1 alpha-stimulated myeloma cells. Therefore rIL-1 alpha stimulates myeloma cells to produce IL-6, which consequently augments proliferation of myeloma cells. Thus, IL-1 can accelerate autocrine growth of myeloma cells through IL-6.
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PMID:Interleukin-1 accelerates autocrine growth of myeloma cells through interleukin-6 in human myeloma. 278 35

Supernatants of freshly isolated human myeloma cell cultures were examined both for bone-resorbing activity (BRA) in vitro using newborn mouse calvaria, and for identification of the causal substances of the BRA. Eight of 14 culture supernatants of myeloma cells had BRA. All of these BRA-positive supernatants were from patients with marked destructive bone lesions of multiple myeloma. The presence of interleukin 1 (IL-1), especially IL-1 beta, was demonstrated in seven of these BRA-positive supernatants but not in BRA-negative supernatants. The concentrations of IL-1 beta were high enough to induce bone resorption in the newborn mouse calvaria assay and the BRA was totally abolished by pretreatment of the supernatants with anti-IL-1 beta antibody but not with either anti-IL-1 alpha antibody or normal serum. Other bone resorbing cytokines such as tumor necrosis factor or lymphotoxin were not present in high enough concentrations to stimulate bone resorption and their levels did not correlate with the BRA. IL-1 beta mRNA was also identified in BRA-positive myeloma cells. These results demonstrate that IL-1 beta is the principal agent of BRA present in supernatants of myeloma cell cultures, and also identify a possible role of IL-1 beta in destructive bone lesions in patients with multiple myeloma.
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PMID:Production of interleukin 1 beta, a potent bone resorbing cytokine, by cultured human myeloma cells. 278 4

Spleens from 1-day-old DBA/2J mice were fused to the nonsecreting myeloma, FO. Dialyzed supernates of these cells were found to suppress the antigen-specific proliferative response of cloned helper or alloreactive T cells at a final concentration of less than or equal to 5%. The same supernate-containing factor did not suppress the response to IL-2 of an IL-2-addicted T cell line. The factor was found not to suppress the production of either IL-2 or antibody, following stimulation of spleen cells with LPS. Absorption analysis revealed that the target of the factor was the accessory cell population. Further experiments indicated that the factor blocked the proliferation of thymocytes due to IL-1. Biochemical analysis revealed a molecular weight for the factor of about 90,000 and a pI of approximately 4.5.
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PMID:NBxFO factor--a novel suppressor factor produced by fusion of neonatal spleen and a nonsecreting myeloma. 297 Mar 5

A variety of types of human B-cell lines were evaluated for their ability to produce interleukin 1 (IL-1)-like factors. All of the eight Epstein-Barr virus (EBV)-transformed B lymphocyte lines, three of four of the EBV+ lymphoma lines, only three of seven of the EBV- lymphoma lines, and none of the three tested myeloma lines secreted some IL-1 activity. The IL-1-like factor produced by the cell lines was detected on the basis of its thymocyte comitogenic and/or fibroblast proliferative activities. Injections of partially purified IL-1-like factor from one of the EBV-transformed B-lymphocyte lines also induced the appearance of an acute phase protein (haptoglobin) in the serum of C3H/HeJ mice. These biological activities are identical with those of monocyte-derived IL-1. Thymocyte comitogenic activity and fibroblast proliferation activity from one of the EBV-B cell line-derived IL-1-like activities were not dissociable by biochemical procedures, including HPLC gel filtration and HPLC anion-exchange chromatography. However, the IL-1-like factor from one of the EBV-B lymphocyte cell lines was larger in size (25 kDa) and more acidic (pI 5.5) than monocyte-derived IL-1.
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PMID:B-cell-derived interleukin-1 (IL-1)-like factor. II. Sources, effects, and biochemical properties. 299 9

The Fc region of Ig is required for numerous biological effector functions which include: opsonization, anaphylaxis, C fixation, catabolism of the Ig molecule, FcR binding, and immune regulation. To this latter point, the cellular and subcellular events involved in immune regulation by IC and Fc fragments of Ig have been the focus of numerous investigations. Characterization of cyanogen bromide cleavage fragments from a human IgG1 myeloma protein indicates that one biologically-active site is found in residues 335-357 of the CH3 domain of the molecule. Synthesis of the biologically-active region resulted in a peptide, termed p23, which stimulates mouse and human B cells to secrete polyclonal Ig and activates AA metabolic pathways. In contrast to these findings, p23 is unable to induce B cell proliferation or IL-1 secretion from macrophages. Analysis of data obtained with overlapping peptides, based on p23, suggests that the minimal active sequence needed for B cell differentiation is leu-pro-pro-ser-arg (residues 351-355). In contrast, only p23 or p23 minus the carboxyterminal glu356 and glu357 were able to induce PGE release. Release of biologically-active peptides derived from the Fc region of Ig into the cellular microenvironment may form the nucleus of a nonspecific in vivo immunoregulatory network. The specificity of peptide regulatory activities could reside in their effectiveness at high concentrations in the cellular microenvironment. The interaction of Fc region peptides with receptors on B cells, T cells, and macrophages/monocytes could result in a dynamic control of immune reactivity.
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PMID:Lymphocyte activation by the Fc region of immunoglobulins. 310 Apr 42

Mice immunized with homogeneous recombinant interleukin-1 alpha (IL-1 alpha) protein developed specific serum titers to the immunogen. Hybridomas resulting from the fusion of the immune spleen or lymph node cells to myeloma cells were analyzed by an antibody capture assay in which the antigen was present in solution. This assay enabled us to isolate two hybridomas secreting antibodies (designated 2F4 and 4G12) that recognized IL-1 alpha and not interleukin-1 beta as judged by the ability of the antibodies to: (a) precipitate IL-1 alpha, (b) inhibit the binding of 125I-IL-1 alpha to the IL-1 receptor on EL4 cells, (c) inhibit the biological activity of IL-1 alpha as measured in a lectin-induced, IL-1-dependent thymocyte proliferation assay. In a double determinant assay configuration, both antibodies, in conjunction with rabbit polyclonal anti-IL-1 alpha antibodies, could detect nanogram concentrations of IL-1 alpha in solution. Cross-inhibition studies indicated that the 2F4 and 4G12 antibodies bind to the same or spatially related epitopes since each can inhibit the binding of the other to IL-1 alpha.
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PMID:Development and characterization of two neutralizing monoclonal antibodies to human interleukin-1 alpha. 325 6

T cell-replacing factor (TRF)/IL-5 is a glycosylated polypeptide that acts as a key factor for B cell growth and differentiation. Since IL-5 action is probably mediated by specific cell surface receptor(s), we have characterized the binding of IL-5 to cells using biosynthetically [35S]methionine-labeled IL-5 and 125I-IL-5 that had been prepared using Bolton-Hunter reagent. The radiolabeled IL-5 binds specifically to BCL1-B20 (in vitro line) (a murine chronic B cell leukemic cell line previously shown to differentiate into IgM-secreting cells in response to IL-5) within 10 min at 37 degrees C. There are two classes of binding sites with high affinity (Kd = 66 pM) and low affinity (Kd = 12 nM) for IL-5 and an average number of binding sites for high affinity and for low affinity were 400 and 7,500 per cell, respectively. The specificity of binding of radiolabeled IL-5 has been confirmed by demonstrating that only unlabeled IL-5 and anti-IL-5 mAb but not by IL-1, IL-2, IL-3, IFN-gamma, and GM-CSF inhibit radiolabeled IL-5 binding to BCL1-B20 cells. Treatment of surface-bound radiolabeled IL-5 with bivalent crosslinkers identified a membrane polypeptide of Mr 46,500 to which IL-5 is crosslinked. A variety of cell types have been surveyed for the capacity to bind specifically radiolabeled IL-5 with high affinity. BCL1 cells MOPC104E (murine myeloma cell line) expressed IL-5-R, whereas BAL. 17 and L10 A (B cell lymphoma) did not. T cell line, mastocytoma cell line, or macrophage tumor cell line did not display detectable levels of IL-5-R. were hardly detectable on normal resting B cells but were expressed on LPS-activated B cells, fitting the function of IL-5 that acts on activated B cells for their differentiation into Ig-secreting cells. Intriguingly, early B cell lines (J-87 and T-88) that grow in the presence of IL-5 expressed significant but low numbers of high-affinity binding sites for IL-5. The biological effects of IL-5 were mediated by high-affinity binding sites. The identification and characterization of IL-5-R should provide new insight into the apparent diverse biological activities of IL-5.
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PMID:Receptors for T cell-replacing factor/interleukin 5. Specificity, quantitation, and its implication. 326 7

It has been shown recently that monocyte-macrophage cells produce a growth factor (HGF) active on newly formed B cell hybridomas. We have studied the effect of HGF on the proliferation of an HGF-sensitive clone of B cell hybridoma. Results obtained showed that the murine P388D1 cell-derived HGF has a m.w. of 29,000 and an isoelectric point (pI) of 6.2 whereas the human monocyte-derived HGF has a m.w. of 34,000 and a pI of 4.9. The HGF activity was not mediated by interleukin 1 because the two activities could be completely separated by gel filtration. Results obtained in in vivo experiments showed that HGF-sensitive cells are tumorigenic in mice. The finding that the HGF biochemical parameters (m.w. and pI) are similar to the ones of a recently described plasmacytoma growth factor suggests that HGF and the plasmacytoma growth factor are similar and that the HGF sensitivity of SP 2/O myeloma cells is reactivated after fusion with normal B lymphocytes.
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PMID:Role of the macrophage-derived hybridoma growth factor in the in vitro and in vivo proliferation of newly formed B cell hybridomas. 349 90

Stable mouse macrophage hybridomas were produced by somatic cell fusion between proteose peptone-elicited peritoneal macrophages and NS-1 myeloma cells. Three cloned hybrid cell lines, designated as N/P-5-3, -6-2, and -7-1, exhibited typical macrophage-like morphology. Moreover, their macrophage characteristics were confirmed by the manifestation of intracellular nonspecific esterase, the detection of Mac-1 antigens and Fc-receptors on the cell surface, and the demonstration of phagocytic and antigen-presenting activities. Furthermore, these cell lines, stimulated with LPS, secreted considerable amounts of a cytotoxic factor and interleukin 1. Cultured cells of various tumor cell lines were sensitive to the cytotoxic factor, but normal thymocytes, spleen cells, and liver cells were not killed by the factor.
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PMID:Mouse macrophage hybridomas secreting a cytotoxic factor and interleukin 1. 387 72

This study documents the autoregulation of B cell growth by an IgM autoantibody. This autoantibody is secreted by B lymphocytes upon stimulation by polyclonal activators and is identified by its potent inhibition of B cell growth induced by these agents (endotoxin, Fc fragment of human gamma-globulin, Mycoplasma bovirhinis, and anti-mouse Ig). The autoantibody specifically affects B cells: there was no effect on mitogen- or antigen-induced T cell proliferation and of responses to interleukin 1, interleukin 2, or interferon. Nonspecific effects were excluded by the ineffectiveness of serum and myeloma IgM. Also, IgG-IgM immune complexes were excluded. The binding specificity of the IgM autoantibody is not yet defined but appears to be a B cell surface structure distinct from membrane Ig. The autoantibody constitutes a ubiquitous, autoregulatory influence on B cell growth, which may be an important component in physiologic and pathologic states of B cell homeostasis.
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PMID:Autoregulation of B cell growth by an immunoglobulin M autoantibody. 387 25


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