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)

A new myeloma cell line designated FLAM-76 was established from a patient with an aggressive nonsecretory plasma cell leukemia. The cell line exhibited morphologic features of flaming cells and contained an abundant eosinophilic cytoplasm with many dilated cisternae of rough endoplasmic reticulum. FLAM-76 cells were positive for cytoplasmic kappa (kapp)-type immunoglobulin but did not secrete it into the culture medium. The cells proliferated in the presence of exogenous interleukin-6 (IL-6) and more than 800 pg/ml of IL-6 was necessary for their continuous growth. The cells did not grow without IL-6, and they did not produce IL-6. Thus, the growth of FLAM-76 appeared to be regulated by the paracrine mechanism of IL-6. Alpha-interferon (alpha-IFN) inhibited the IL-6-dependent growth of FLAM-76 in doses greater than 1000 U/ml. FLAM-76 cells expressed CD38 (OKT10) and cell adhesion-associated antigens such as CD44 and CD54 (ICAM-1). Chromosome analysis revealed FLAM-76 to have a hypodiploid chromosome constitution with t(11;14)(q13;q32) abnormality, which frequently is seen in neoplasms of B-cell origin. Immunoglobulin (JH and Ck) gene rearrangement (but no BCL-1 gene rearrangement) was found in this cell line.
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PMID:The establishment of an interleukin-6-dependent myeloma cell line (FLAM-76) carrying t(11;14)(q13;q32) chromosome abnormality from an aggressive nonsecretory plasma cell leukemia. 151 3

Most of the circulating lymphocytes from three asymptomatic adults (one male, two female, age range 61-67 years) with isolated persistent lymphocytosis of between 7.1 and 10 x 10(9)/l possessed characteristic villous projections of the cell membrane. Morphological, histochemical, ultrastructural, immunological, and genotypic studies confirmed a clonal proliferation of tartrate-resistant acid phosphatase (TRAP)-negative CD5-CD10-CD25- and CD11c+ B-cells. In addition to CD11c, these cells expressed other adhesion receptors (LFA-1/CD11a, VLA-4/CD29/49d, ICAM-1/CD54, and LAM-1) and produced detectable amounts of interleukin-1 beta, interleukin-6, and in one case tumour necrosis factor-alpha mRNA. This monoclonal villous lymphocytosis (MVL) could be differentiated from B-cell chronic lymphocytic, prolymphocytic, and hairy cell leukaemias, and from previously recognized CD11c+ chronic B-cell leukaemia. A rare splenomegalic non-Hodgkin's lymphoma variant with circulating villous B-lymphocytes (SLVL), usually CD10+ and sometimes CD11c- and TRAP+, appears to be a closely related disorder. In all three patients the lymphocyte count increased very slowly, at a rate less than 5 x 10(9)/l per year, over 3-7.5 years of follow up, and a moderate splenomegaly eventually developed in one of the patients. Chemotherapy was never required. MVL may be a relatively benign clinical entity akin to SLVL within the group of CD11c+ B-cell lymphoproliferative disorders.
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PMID:Monoclonal lymphocytosis with villous lymphocytes: a chronic lymphoproliferative disease of CD11c+ B-cells. 168 36

Psoriasis is characterized by epidermal hyperplasia, altered epidermal maturation, and local accumulation of acute and chronic inflammatory cells. Keratinocyte hyperplasia in psoriasis may be explained in part by overproduction of growth factors or cytokines which stimulate epidermal proliferation and by altered metabolism of growth-factor receptors in affected skin. Psoriatic epidermis displays overproduction of TGF-alpha and interleukin-6 (IL-6), factors produced by keratinocytes and other cell types in psoriatic skin. TGF-alpha and IL-6 are mitogens for normal human keratinocytes and act via specific receptors. The TGF-alpha receptor (EGF receptor) is overexpressed in psoriatic epithelium and its altered expression could be caused in part by gamma interferon which prevents normal receptor down-regulation in response to EGF binding. Several phenotypic features of the psoriatic keratinocyte, including growth activation and expression of HLA-DR, gamma-IP-10, ICAM-1, and other molecules, are best explained as resulting from the combined effects of TGF-alpha, IL-6, and gamma interferon (and possibly other cytokines) on epidermal keratinocytes. The multiple histologic features of psoriasis, including epidermal hyperplasia and accumulation of acute and chronic inflammatory cells, may be mediated by defined growth factors and cytokines that are produced in psoriatic skin and affect the function of diverse cell types.
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PMID:Role of growth factors, cytokines, and their receptors in the pathogenesis of psoriasis. 216 87

Our studies in vitro demonstrate that neutrophil mediated injury of isolated cardiac myocytes requires the presence of ICAM-1 on the surface of the myocyte and CD11b/CD18 activation on the neutrophil. In post-ischemic cardiac lymph, there is rapid appearance of C5a activity during the first hours of reperfusion. Interleukin-6 activity is present throughout the first 72 h of reperfusion and is sufficient to induce ICAM-1 on the surface of the cardiac myocyte. In situ hybridization studies suggest that ICAM-1 mRNA is found in viable myocardial cells on the edge of the myocardial infarction within 1 h of reperfusion. ICAM-1 protein expression on cardiac myocytes is seen after 6 h of reperfusion, and increases thereafter. Non-ischemic tissue demonstrates no early induction of ICAM-1 mRNA or ICAM-1 protein on myocardial cells. In our most recent experiments, we have determined that reperfusion is an absolute requirement for the early induction of myocardial ICAM-1 mRNA in previously ischemic myocardial cells. To further assess this, we have cloned and sequenced a canine interleukin-6 (IL-6) cDNA. The data suggest that early induction of IL-6 mRNA is also reperfusion dependent as it could be demonstrated in the same ischemic and reperfused segments in which ICAM-1 mRNA was found. Peak expression of IL-6 mRNA occurred much earlier than that for ICAM-1 mRNA. Similar experiments were then performed with a molecular probe for interleukin-8 (IL-8). This chemokine is a potent neutrophil stimulant and has a higher degree of specificity for neutrophils than classic chemoattractants such as C5a.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of early reperfusion in the induction of adhesion molecules and cytokines in previously ischemic myocardium. 749 54

Human monoclonal IgM antibody HA-1A, which recognizes the lipid A component of bacterial lipopolysaccharide (LPS), has been shown to reduce mortality in Gram negative septicemia. The vascular endothelial lining of blood vessels, which controls leucocyte traffic and activation, as well as haemostatic balance, may be one of the primary targets of LPS action during sepsis. In earlier studies we have described HA-1A-induced immune adherence of LPS to complement receptors on erythrocytes, and showed that pre-incubation with HA-1A, in the presence of complement and red blood cells, markedly reduced LPS-induced cytokine production from peripheral blood mononuclear cells. In the present study, we measured the effect of immune adherence of LPS in the presence of HA-1A on the responses of cultured endothelial cells, and found that subsequent expression of adhesion molecules such as E-selectin, ICAM-1 and VCAM-1, and secretion of the cytokines interleukin-6 and granulocyte-macrophage colony stimulating factor were markedly reduced. Moreover, the ability of LPS to increase levels of tissue factor procoagulant activity on endothelial cells was markedly diminished by LPS immune adherence to HA-1A. This decrease in endothelial activation in response to LPS following immune adherence to HA-1A may play a significant role in the protective effect of HA-1A in vivo during the course of Gram negative sepsis.
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PMID:Antilipid A monoclonal antibody HA-1A decreases the capacity of bacterial lipopolysaccharide to activate human vascular endothelial cells by an immune adherence mechanism. 751 52

Polyinosinic:polycytidylic acid (poly I:C) is a synthetic double-stranded polyribonucleotide that elicits immune responses analogous to those observed during viral infection. It is also known to modulate the expression of certain autoimmune disorders including diabetes mellitus in the BB rat and NOD mouse. The mechanism underlying these immunomodulatory effects is not known, but it could involve activation of vascular endothelium. We now report that parenteral poly I:C induces rat pancreatic endothelium to hyperexpress intercellular adhesion molecule 1 (CD54). This is accompanied by a perivascular recruitment of mononuclear cells to the exocrine pancreas. Corollary in vitro studies demonstrated that poly I:C is a potent activator of both rat and human endothelial cells in culture. It upregulates endothelial expression of several leukocyte adhesion molecules, stimulates the release of interleukin-6 and interleukin-8, and antagonizes interferon-gamma induction of major histocompatibility complex class II expression. We conclude that poly I:C activates endothelial cells to express surface molecules and cytokines in a pattern classically associated with leukocyte recruitment. These effects may in part contribute to the immunomodulatory effects of poly I:C in animal models of autoimmunity.
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PMID:Polyinosinic:polycytidylic acid is a potent activator of endothelial cells. 751 92

Odontogenic cysts are one of the commonest bone destroying lesions of the maxillofacial skeleton, with the inflammatory radicular cyst being the commonest jaw cyst. Explants of radicular cysts produce an interleukin-1-like activity which could explain the osteolysis seen with these tumours though the cellular source of this osteolytic activity is unknown. In the present study, cytokines with known inflammatory and osteolytic activity: interleukin-1 (IL-1), tumour necrosis factor (TNF), interleukin-6 (IL-6), and the chemotactic cytokine interleukin-8 (IL-8) have been localized immunocytochemically in radicular cysts. The cellular adhesion receptors ICAM-1 and ELAM-1 have also been immunolocalized. All specimens showed positive staining for IL-1 (alpha and beta) and IL-6, with these cytokines being located in epithelial and vascular endothelial cells. Only two specimens demonstrated TNF and IL-8 staining, which was located in macrophages. All specimens demonstrated ELAM-1 staining in endothelium and ICAM-1 staining in epithelium, endothelium and mononuclear cells. These findings show that radicular cysts contain two bone-modulating cytokines, IL-1 and IL-6, and that these appear to be synthesized mainly by the epithelial cells. Cysts also contain a proportion of activated blood vessels whose endothelial cells express the cellular adhesion receptors ICAM-1 and ELAM-1.
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PMID:Immunocytochemical localization of inflammatory cytokines and vascular adhesion receptors in radicular cysts. 768 27

Bone marrow-derived cells from patients suffering from paroxysmal nocturnal hemoglobinuria (PNH) show a defect in the expression of phosphatidylinositol-anchored membrane proteins, including the CD14 molecule. Blocking experiments with anti-CD14 monoclonal antibodies have shown that lipopolysaccharide (LPS)-induced tumor necrosis factor alpha production by monocytes depends on the interaction between CD14 and a complex formed by LPS and LPS-binding protein. We used a whole-blood model to examine the LPS-induced production of tumor necrosis factor alpha and interleukin-6 in PNH patients and healthy volunteers. At low endotoxin concentrations (1 ng/ml), PNH patients displayed a marked defect in the production of both cytokines, whereas at high LPS concentrations (100 ng/ml), cytokine production was similar to that in healthy volunteers. Using flow cytometry, we also studied the expression of the adhesion molecules Mac-1 (CD11b/CD18) and ICAM-1 (CD54) by monocytes and granulocytes after LPS stimulation. Compared with phagocytes from healthy volunteers, CD14-deficient cells showed poor Mac-1 and ICAM-1 upregulation when whole blood was stimulated with LPS (1 ng/ml), whereas their response to higher LPS doses (100 and 1,000 ng/ml) was essentially normal. The importance of the CD14 molecule in the activation of phagocytes by low LPS concentrations was confirmed by the inhibitory effect of an anti-CD14 antibody both in healthy volunteers and in PNH patients. Since these patients produce the soluble form of the CD14 molecule, these data suggest that soluble CD14 could play a role in phagocyte responses to LPS. We conclude that, in whole blood, phagocytes from PNH patients show impaired responsiveness to LPS and this phenomenon is most probably related to their defect in expression of membrane CD14.
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PMID:Impaired phagocyte responses to lipopolysaccharide in paroxysmal nocturnal hemoglobinuria. 769 46

Human activated T cells adhere to synovial fibroblast-like cells in vitro. The present study was conducted to investigate the consequences of T cell-synovial fibroblast interactions with regard to induction of adhesion molecules and proinflammatory cytokines. A sensitive Western blot technique, polymerase chain reaction (PCR) amplification, and fluorescence-activated cell sorter (FACS) analysis were used to analyze the induction of VCAM-1 and ICAM-1 expression in T cell-synovial fibroblast cocultures. VCAM-1 and ICAM-1 expression could be induced in synovial fibroblast-like cells by 2 h. PCR amplification showed that both forms of VCAM-1 mRNA are found after the interaction of synovial fibroblasts with T cells. Up-regulation of VCAM-1 and ICAM-1 was confined to synovial fibroblasts; T cells did not express VCAM-1 or increased ICAM-1. In contrast to the T cell-synoviocyte interaction, the interaction between T cells and dermal fibroblasts resulted in the up-regulation of ICAM-1 but not VCAM-1, suggesting tissue-specific regulation of VCAM-1. The T cell-synovial fibroblast interaction also resulted in increased levels of tumor necrosis factor (TNF), interferon-gamma, and interleukin-6 in coculture supernatant. Of the neutralizing antibodies used against these cytokines, only anti-TNF could significantly inhibit VCAM-1 and ICAM-1 expression. When T cells were separated from synoviocytes by a chamber that allowed medium exchange but no cell contact, VCAM-1 and ICAM-1 failed to be up-regulated and cytokine accumulation in cocultures was drastically reduced. Our results demonstrate mutual cell activation of T cells and synoviocytes upon cell contact as shown by the release of T cell- and synoviocyte-specific cytokines and suggest a cell contact-mediated and T cell-initiated mechanism for the chronic accumulation and retention of mononuclear cells via VCAM-1/ICAM-1 by synovial fibroblasts in the rheumatoid synovium.
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PMID:Cell contact between T cells and synovial fibroblasts causes induction of adhesion molecules and cytokines. 769 40

A 75-year-old female was diagnosed as having multiple myeloma (IgG.lambda type. Stage IIA) with plasmacytoma of the head and back in October, 1989. She obtained partial remission by MCNU and MP therapy, but relapsed with massive ascites in January, 1991. VAD therapy was not effective and she died of multiple organ failure on February 23. Her ascites contained a large number of myeloma cells, and the phenotypic analysis and the response to interleukin-6 (IL-6) of these myeloma cells were examined. The myeloma cells were positive for CD33, CD45, CD45RA, CD63, CD71, plasma cell associated antigens such as CD38, PCA-1, BL3, and various kinds of adhesion molecules: CD11a/CD18 (LFA-1), CD29 (VLA-beta 1), CD44 (H-CAM), CD49d (VLA-4), CD54 (ICAM-1), CD56 (N-CAM), CD58 (LFA-3). IL-6 level in the ascites was increased at 91.0pg/ml. The myeloma cells showed an IL-6 dependent growth, which was inhibited by anti-IL-6 antibody (Ab) and anti-IL-6 receptor Ab in vitro. Myeloma cells appearing in ascites have rarely been reported. Our case suggested that IL-6 was a potent growth factor of myeloma cells through an autocrine mechanism in the ascites, and resulted in an aggressive myeloma.
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PMID:[Multiple myeloma with massive ascites fluid--immunophenotypic analysis of myeloma cell and its IL-6-dependent growth]. 786 16


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