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)

Interleukin-6 (IL-6) is a multifunctional cytokine that participates in the inflammatory and immune responses. In human skin, keratinocytes produces IL-6, although the in vivo role of this cytokine is unknown. In the present study we investigated the in situ localization of IL-6 in normal epidermis (n = 10) and in a group of skin diseases characterized by epidermal atrophy. Formalin-fixed paraffin-embedded skin biopsies from patients with clinical and histopathological features consistent with localized scleroderma (n = 10), systemic scleroderma (n = 5), lichen sclerosus et atrophicus (n = 9) and balanitis xerotica obliterans (n = 7) were tested using polyclonal antibodies and avidin-biotin-peroxidase immunostaining. We demonstrated the presence of IL-6 in normal epidermis and in atrophic skin diseases. In normal skin there was moderate intercellular and intracellular reactivity detected using a high antibody concentration. In specimens with epidermal atrophy we detected intense cytoplasmic and intercellular immunostaining using a lower antibody concentration. The immunoreactivity was independent of the epidermal thickness. Plasma IL-6, measured by radioimmunoassay, was not elevated in plasma from patients with localized or systemic scleroderma. Increased IL-6 in the epidermis of selected skin diseases suggests that IL-6 may be related to the pathophysiology of dermatologic diseases characterized by epidermal atrophy.
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PMID:In situ localization of interleukin-6 in normal skin and atrophic cutaneous disease. 134 91

Although hematopoietic growth factors influence renewal and differentiation of blast progenitors in acute myelogenous leukemia (AML), morphological maturation of leukemic blasts is thought a rare event, even when cultured in the presence of appropriate growth stimulants. However, light microscopic observation may not be sufficient to clarify precisely the effects of hematopoietic growth factors on the morphological differentiation of leukemic blasts. In this study, using cell culture techniques and electron microscopic cytochemistry for platelet peroxidase (PPO), we studied the effects of interleukin-3 (IL-3) and interleukin-6 (IL-6), both of which are considered to play an important role in normal megakaryocytopoiesis, on the growth and differentiation of blast cells from two patients with childhood acute megakaryoblastic leukemia (AMKL). In both of the two cases, IL-3 stimulated leukemic colony formation in methylcellulose culture, whereas IL-6 showed little such activity. However, in suspension culture, IL-6 was active in promoting megakaryocytic differentiation, although incomplete, as detected by increase in the number of PPO-positive cells, some having demarcation membrane-like structure. This effect was evident in culture with IL-6 alone in one patient, but it was detectable only when IL-6 was used in combination with IL-3 in the other patient. In contrast, IL-3 alone stimulated differentiation towards myeloid but not megakaryocytic lineage. These results indicate that IL-3 and IL-6 have a distinct role in leukemic megakaryocytopoiesis (IL-3 stimulates growth, whereas IL-6 promotes morphological differentiation) and that cooperation between these two cytokines functions most effectively for megakaryocytic differentiation of AMKL cells in a fashion similar to that for normal megakaryocytopoiesis.
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PMID:Differentiation induction of blast cells in two cases of childhood acute megakaryoblastic leukemia in vitro by interleukin-3 and interleukin-6: an ultrastructural cytochemical study. 165 16

Evidence has accumulated in the last few years that the expression of the microsomal/peroxidase antigen (M/TPO-Ag) in thyroid cells is induced by TSH, through pathways which involve intracellular cAMP accumulation and protein synthesis. These data have been found true in any thyroid system studied so far, both in terms of immunologic and enzymatic activity of TPO. TSH and cAMP also increase the levels of the specific mRNA for TPO in thyroid cells from different species. Whether this phenomenon is due to a direct transcriptional regulation of the TPO gene, as shown in dog thyroid cells, or to posttranscriptional effects, as it would appear in FRTL-5 cells, remains to be clarified by future experiments. Thyroid stimulating antibody (TSAb) of Graves' disease also stimulates the expression of M/TPO-Ag. This finding gives further support to the relevance of TSAb in the pathogenesis of hyperthyroidism and explains the well known observation that the "microsomal" antigen is particularly abundant in glands of Graves' patients. The modulation of M/TPO-Ag surface expression by TSH can explain the decrease of circulating anti-MAb observed during L-thyroxine therapy in hypothyroid patients with Hashimoto's thyroiditis. Other agents, such as methimazole and sodium iodide, which influence thyroid cell function, do not directly interfere with the expression of M/TPO-Ag. Cytokines, such as gamma-interferon, interleukin-1, and interleukin-6 have been shown to inhibit the TSH-induced increase of TPO mRNA, but further investigations are required to elucidate the exact role of cytokines in the regulation of M/TPO-Ag expression.
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PMID:The microsomal/peroxidase antigen: modulation of its expression in thyroid cells. 166 95

Experiments in rats suffering from primary acute adjuvant inflammation showed independent changes in serum acute phase protein concentration and macroscopic paw inflammation during antiinflammatory treatment: soybean trypsin inhibitor and horse-radish peroxidase caused antiinflammatory effects but simultaneously produced increased alpha 2 macroglobulin levels. On the other hand, cycloheximide significantly inhibited the increase of alpha 2 macroglobulin concentration in adjuvant inflammation, however, it had no antiinflammatory effect. All forms of treatment caused even some change in protein plasma levels of healthy rats which probably relates to an activation of cells producing interleukin-1, interleukin-6, and/or hepatocyte stimulating factor which trigger the synthesis of acute phase proteins in the liver. In inflamed rats, the snake venom batroxobin caused a significant decrease in the fibrinogen level whereas the paw swelling remained completely unaffected. Therefore, it seems to be doubtful whether acute phase proteins essentially contribute to the modulation of acute inflammatory reaction in primary rat adjuvant inflammation.
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PMID:Acute phase reaction in rats: independent change of acute phase protein plasma concentration and macroscopic inflammation in primary rat adjuvant inflammation. 169 77

The presence of human cytokines was examined in parallel skin biopsies and epidermal single cell preparations obtained from normal individuals. Using biotin-avidin-peroxidase and immunofluorescence techniques and antibodies against recombinant cytokines, a granular intercellular/membrane-associated staining for interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF alpha), but not IL-1 alpha or beta, was observed. An epidermal cytoplasmic staining pattern was also detected, which was most pronounced using the anti-rIL-6 antiserum. In the epidermal single cell preparations, membrane-associated staining was detected for both IL-6 and TNF alpha. Double staining revealed that CD1-positive Langerhans cells (LC) failed to express any of the examined cytokines. In vitro binding of rIL-6 or rTNF alpha to skin sections and epidermal single cell preparations indicated that the cell surface-associated IL-6 and TNF alpha originally demonstrated on keratinocytes were truly membrane-bound. Finally, co-cultivation of epidermal cells with an IL-6 responsive cell line, B9, and testing of epidermal cell supernatants in this assay, indicated that the in vivo membrane-bound IL-6 had biological activity.
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PMID:Interleukin-6 and tumour necrosis factor alpha are expressed by keratinocytes but not by Langerhans cells. 170 42

To identify viral antigens, the types of infiltrating mononuclear cells and cytokine bearing cells, the frozen brain tissue sections form a patient with herpes simplex encephalitis who died on 12th hospital days, were examined by immunocytochemistry methods and combined immunocytochemistry and in situ hybridization. The avidin-biotin peroxidase complex (ABC) techniques were applied for the detection of antigens. All monoclonal antibodies to Leu series and polyclonal antisera to lymphotoxin (LT), interleukin-6 (IL-6) and interferon-gamma (IFN-gamma) were purchased form Becton Dickinson Co., and Genzyme Co., (USA) respectively. A large number of neurons and glial cells staining positively HSV-1 antigens were found in the gray matter. Moreover, although a moderate number of HLA-DR (Ia) positive cells were found in the parenchyma, there were few cells displaying positively for Leu-3a, Leu-2a and Leu-7 respectively. To evaluate the number of positive cells appeared in the brain tissues, Leu stain for 4, 2a, 3a, 7, 12 and HLA-DR demonstrated 1.6%, 0.4%, 0.9%, 0.7% and 10% respectively. In addition, numerous number of IFN-gamma positive cells were detected around the lesion and randomly distributed thoroughly the lesion. IL-6 positive cells and LT positive cells were also similar in distribution to IFN-gamma positive cells. Moreover, in simultaneous detection of HLA-DR and HSV-1 mRNA by the combined immunocytochemistry and in situ hybridization, there were seen glial cells staining positively for HLA-DR (Ia) and several cells with mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The detection and quantitative analysis of viral antigens, infiltrating mononuclear cells, IFN-gamma, LT and IL-6 bearing cells in the frozen brain tissue sections from a patient with herpes simplex encephalitis by immunocytochemistry]. 216 12

We have investigated the effect of transforming growth factor-beta 1 (TGF-beta 1) and three cytokines on expression of antioxidative enzymes, manganese-superoxide dismutase, copper, zinc-superoxide dismutase, and catalase in cultured hepatocytes of rat. While interleukin-1 beta and interleukin-6 induced manganese-superoxide dismutase gene expression, they slightly suppressed catalase gene expression in rat hepatocytes. TGF-beta 1 suppressed expression of all these antioxidative enzymes in time- and cell density-dependent manners. Furthermore, we examined the effect of TGF-beta 1 on expression of glutathione peroxidase and glutathione-S-transferase, which exhibit glutathione-dependent peroxidase activity in rat hepatocytes. Expression of two major classes of the rat glutathione-S-transferase subunits 1 and 2 was also reduced by TGF-beta 1, although expression of glutathione peroxidase was not affected. Flow cytometric analysis indicated that production of peroxides was increased in hepatocytes treated with TGF-beta 1. These data suggest that augmented production of hydrogen peroxide and its intermediate through suppression of antioxidative enzyme expression may participate in cellular injury or growth inhibition promoted by TGF-beta 1.
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PMID:Suppression of antioxidative enzyme expression by transforming growth factor-beta 1 in rat hepatocytes. 751 58

A new human multilineage myeloid leukemia cell line, MHH225, has been established in our laboratory from the bone marrow of a 60-year-old patient suffering from acute megakaryoblastic leukemia (M7); it provides a unique model for studying the effect of biologic and chemical agents on the lineage specificity of a multipotent myeloid leukemia clone containing a mixed population of megakaryoblast, erythroblast, and myeloblast cells in a serum-free culture. Morphologically, all 225 cells are large blast cells with basophilic cytoplasm containing no granules, large round nucleus containing 2-3 prominent nucleoli, and fine chromatin structure and a large nuclear/cytoplasm ratio. The MHH225 cells are CD34+HLA-DR+CD33+CD13+ with 57.6%, 28.3%, and 7.8% of them being CD41+, glycophorin A+, and CD15+, respectively, and all lymphoid-specific antigens are negative. The karyotype analysis of MHH225 cells revealed a deletion of the short arm of chromosome 7: del(7)(p13)-, a whole-arm translocation between the long arms of chromosomes 9 and 21: t(9;21)(q10;q10), and a chromosome 11 with an elongated long arm due to duplication of chromosome 11 material as well as to translocation of part of chromosome 9 onto 11q+. Also, chromosome 21 was deleted in some metaphases or showed a ring formation in other metaphases. Utrastructurally, MHH25 cells display a strong platelet peroxidase activity in the nuclear envelope and the endoplasmic reticulum. The MHH25 cells have been grown exponentially without growth factors or conditioned media or serum only in RPMI1640 culture medium. None of the myelopoietic growth factors, i.e., interleukin-3, GM-CSF, G-CSF, erythropoietin, or interleukin-6, has any effect on the proliferation and differentiation of MHH25 cells. The two, hematopoietic inhibitory cytokines, interferon-alpha and tumor necrosis factor-alpha, have only minimal growth inhibitory effect. Stem cell factor showed only weak growth-stimulatory effect on MHH225 cells but significantly inhibited chemotherapy-induced apoptosis in these cells. The new cell line MHH225 should constitute a useful model for studying stem cell antigen (CD34)-positive human multilineage myeloid leukemia cells carrying a deletion in the short arm of chromosome 7 and an aberration in chromosome 11 and provide a unique tool for investigating human hematopoietic stem cell biology and its cytokine regulation in serum-free cultures. To our knowledge, the MHH225 cell line is the first human CD34-positive leukemia cell line growing in serum-free cultures to be established.
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PMID:Establishment and characterization of a novel CD34-positive human myeloid leukemia cell line: MHH225 growing in serum-free culture. 754 28

We have established a novel human megakaryoblastic cell line, designated as MEG-A2, from a patient with megakaryoblastic crisis of Philadelphia (Ph) chromosome positive chronic myelogenous leukemia. MEG-A2 cells showed positive phenotypes for periodic acid Schiff and alpha-naphthylbutyrate esterase reactions, but were negative for myeloperoxidase and naphthol ASD chloroacetate esterase reactions. Flow cytometric analyses of cell surface markers revealed that MEG-A2 cells had a low level of GP IIb/IIIa expression as well as apparent expressions of CD4, CD7, CD13, CD33 and CD34 antigens, but no expression of GP Ib nor glycophorin A. Stimulation with phorbol 12-myristate 13-acetate (PMA) dramatically increased the expression of megakaryocyte-related markers such as HPL-3, J15, Pit-1, Y2/51 and AN51 in MEG-A2 cells. The PMA-stimulation also induced expression of platelet peroxidase (PPO) in MEG-A2 cells on electromicroscopic observation. Proliferative responses to granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3) or erythropoietin were observed, and the expression of GP IIb/IIIa was increased by stimulation with GM-CSF, IL-3, erythropoietin and interleukin-6 (IL-6). Protein S mRNA expression was seen in cultured cells on Northern blot analysis. Expression of platelet factor 4 mRNA was induced in PMA-stimulated cells, and a marked accumulation of protein was observed in the culture medium. In conclusion, a new cell line, MEG-A2, belongs to the relatively immature megakaryocytic lineage and has markedly increased megakaryocytic characteristics with PMA stimulation.
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PMID:Establishment and characterization of an immature human megakaryoblastic cell line, MEG-A2. 786 73

Murine retinal glia are normally negative for major histocompatibility complex (MHC) Class II antigens and express low levels of MHC Class I and intercellular adhesion molecule-1 (ICAM-1) as detected by avidin-biotin-peroxidase immunohistochemistry. These surface molecules associated with immune function were either induced (Class II) or upregulated (Class I and ICAM-1) on cultured retinal glial cells in a dose- and time-dependent manner following exposure to recombinant interferon-gamma (rIFN-gamma). MHC Class I and II expression by passaged and primary cells was maximal (> 90% positive) after incubation with 100 U/m1 of rIFN-gamma for 48 h. ICAM-1 expression by primary and passaged cells tripled between 48 and 72 h after exposure to 25 or 50 U/m1 of rIFN-gamma. By 72 h after exposure to 100 U/m1 of rIFN-gamma, 62% of the retinal glia were positive for ICAM-1, whereas under normal culture conditions these molecules were detected on < 3% of the retinal glia. Bacterial lipopolysaccharide (LPS), a known stimulator of central nervous system (CNS) astrocytes, increased ICAM-1 expression only 3-fold to 9% of cells staining positively, but neither MHC Class I nor Class II expression was altered from baseline levels. Surface expression of ICAM-1, MHC Class I, and MHC Class II was unaffected by exposure to either rTNF-alpha (1000 U/m1) or rIL-6 (100 U/m1) for 24 h. Under normal culture conditions, intracellular interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were detected immunohistochemically. Exposure to either rIFN-gamma or LPS induced more intense staining which correlated with increased secreted levels of both cytokines in culture supernatants. Levels of secreted TNF-alpha increased 6-fold after stimulation with LPS for 24 h, while secreted IL-6 increased over 9-fold. These results support the hypothesis that retinal glia may participate in intraretinal immune processes following stimulation during inflammatory and infections processes via either cell surface-or soluble mediator-dependent mechanisms or a combination of both.
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PMID:Modulation of immune-associated surface markers and cytokine production by murine retinal glial cells. 859 92


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