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)

Human C-reactive protein (CRP) is the major acute phase reactant during acute inflammation. The human CRP promoter is expressed in an inducible and cell-specific manner when linked to the bacterial CAT gene and transfected into human hepatoma cell cultures. In this paper we analyze the effect of several recombinant cytokines or CRP promoter inducibility in human Hep3B cells. When cytokines are tested singly the major inducer of CRP-CAT fusions is interleukin-6 (IL-6). Maximal CAT gene expression, however, is only achieved when both interleukin-1 beta (IL-1 beta) and IL-6 are present. The response to the two cytokines is cooperative. Cooperativity is maintained when the CRP promoter is linked to a different coding region, that of the bacterial neomycin phosphotransferase II gene. With a series of 5' and 3' deletions we show the existence of two distinct and independent regions responsive to IL-6 and located upstream to the TATA box. The IL-1 effect is exerted at the level of downstream sequences that are probably important for optimal mRNA translatability or nuclear-cytoplasmic transport. Inducibility is not influenced by the activation of protein kinases C or A and does not require new protein synthesis.
EMBO J 1989 Dec 01
PMID:Dual control of C-reactive protein gene expression by interleukin-1 and interleukin-6. 255 73

An overall increase of 40% in nuclear-associated protein has been shown to be one of the sequellae of exposure of eukaryotic cells to elevated temperatures. Several investigators have shown that the increased protein/DNA ratios correlated well with the degree of cytotoxicity. In previous investigations, we have shown that cycloheximide, which protects the cell from the killing effects of heat, produces a dramatic reduction of the bulk nuclear-associated proteins after heating. In this investigation, we studied a previously unobserved efflux of a 26 kDa protein after heat shock and the preferential accumulation of the 70 kDa protein. The 26 kDa protein was shown not to be a member of previously described heat shock protein families. Preferential reduction of a 26 kDa protein and accumulation of a 70 kDa protein was observed in nuclei isolated from Chinese hamster ovary cells after heating at 43 degrees C. After heat treatment, the 26 kDa protein in the nucleus was decreased to a level 0.1-0.3 times the original amount in unheated cells, and the 70 kDa protein in the nucleus increased by a factor of 1.6-1.8. The normal levels of these two proteins were restored when cells were incubated at 37 degrees C following heat shock. Cells treated with heat protectors, cycloheximide and histidinol, demonstrated approximately the same redistribution in nuclear 26 and 70 kDa proteins immediately after heating as those not exposed to these drugs. On the other hand, restoration to control levels was much faster in the protector-treated cells, suggesting that "repair" of heat-induced damage is an important factor in the cells ability to survive this insult. Return to normal protein levels did not require new protein synthesis.
J Cell Physiol 1989 Dec
PMID:Heat protectors and heat-induced preferential redistribution of 26 and 70 kDa proteins in Chinese hamster ovary cells. 259 26

The molecular mechanism of the interleukin (IL) 2-induced differentiation of human B cells has been investigated. The experimental results show that Staphylococcus aureus Cowan strain I (SAC) activation alone induces IL6 secretion from B cells. When B cells were activated by SAC, there was an increased transcription of the IL6 mRNA. It reached the peak level by 6 h and rapidly decreased to an undetectable level within 24 h. The IL6 concentration in the culture supernatants reached the peak at 24-48 h and decreased slightly in the following culture periods. Since IL 2 alone could induce IgG secretion, whether exogenous IL6 was added or not, and IL2 did not increase autocrine IL6 synthesis, it appears that IL2 induces the IL6 responsiveness of SAC-activated B cells to differentiate in the later stage of the culture. The addition of polyclonal anti-IL6 antibody inhibited IgG secretion. The antibody still efficiently blocked IgG secretion up to day 5, indicating an important role of autocrine IL6 in the IL2-driven B cell differentiation. However, the saturation dose of anti-IL6 antibody inhibited 50%-70% of IgG secretion, suggesting that IL2-induced B cell differentiation appears to be mediated by other factors besides IL6.
Eur J Immunol 1989 Dec
PMID:Recombinant interleukin (IL) 2-induced human B cell differentiation is mediated by autocrine IL6. 260 40

Early 4-hydroxyperoxycyclophosphamide (4-HC) resistant hematopoietic progenitor cells (pre-colony-forming units, pre-CFU) were evaluated by a two-step liquid culture system, (earlier progenitors), pre-CFU, as well as by the conventional semi-solid mixed colony assay (later progenitors) for their growth response to interleukin-6 (IL-6), interleukin-3 (IL-3), and a combination of both factors. The effect of the IL-6/IL-3 combination was compared to that of IL-1/IL-3. IL-3 alone proved less effective in supporting earlier pre-CFU cells than later progenitor cells. In a previous work IL-6 promoted the growth of early multipotential progenitor cells circulating in hairy cell leukemia (HCL) patients. IL-6 alone did not stimulate growth of either early or later normal progenitor cells. However, a significant synergistic effect was obtained when IL-6 and IL-3 were added together (p less than 0.05). IL-6/IL-3 synergism was more potent than IL-1/IL-3 in promoting growth of colonies. The previously described synergistic effect of IL-1/IL-3 seems to be independent of IL-6. Thus, our results suggest that the multi-functional cytokine IL-6, may be of use in shortening the engraftment time in bone marrow transplantation.
Scanning Microsc 1989 Dec
PMID:Interferon beta 2/interleukin-6 and interleukin-3 synergize in stimulating proliferation of human early hematopoietic progenitor cells. 263 33

An assay system was developed to measure feline hybridoma growth factor (HGF)/interleukin-6 (IL-6) activity in biological samples containing many kinds of cytokines by using the proliferation of the newly established mouse-rat hybridoma clone, B3B1. The proliferative response of this B3B1 clone was IL-6-specific, and could not be promoted by other cytokines including IL-1, IL-2, IL-3, and granulocyte-colony-stimulating factor (G-CSF). The anti-human B-cell stimulatory factor 2 (BSF-2)/IL-6 antiserum did not neutralize feline HGF/IL-6 activity in conditioned media prepared from feline con A-stimulated splenocytes and unstimulated alveolar macrophages, indicating antigenic differences between species. Feline HGF/IL-6 was eluted into the fractions corresponding to a molecular weight of 30,000-40,000 in gel filtration, and into the fractions at a salt concentration of 0.2-0.3 M NaCl in anion exchange chromatography. The physicochemical properties of feline HGF/IL-6 were slightly different from those of murine and human IL-6.
J Leukoc Biol 1989 Dec
PMID:Feline hybridoma growth factor/interleukin-6 activity. 268 91

The number of cytokine molecules identified and cloned grows almost weekly. Studies using pure preparations have shown that single entities, e.g. TGF beta and IL-1 act on a wide variety of target cells whereas other cytokines, e.g. G-CSF have a more restricted target cell population. The outcome of stimulation of a cell by a cytokine depends on the target cell type, the presence of other coexisting cytokines and, as the release of cytokines may be targeted in the direction of the stimulus, the orientation of producer and target cells. These modulating phenomena may enable a small number of cytokines to specifically define a much larger number of responses, so that maximum 'value' is obtained from the successful evolution of cytokine and receptor molecules. The current nomenclature has little regard for this, the names of cytokines often deriving from the first property observed in vitro. In many cases these are not the most important properties of the molecule and can be misleading, e.g. transforming growth factor beta, which is growth inhibitory in some systems; the antiviral action of interferon gamma is relatively minor compared to its role as a macrophage activation factor; and interleukin-1 is produced by, and acts on, many cells outside the lymphohaemopoietic system. In addition, although there is often a high degree of homology, the repertoire of activities may vary between species. For example, IL-5 is a growth factor for eosinophils, both in humans and mice, however, in the mouse it also acts as a B-cell differentiation factor--a property which has been less easy to identify in human IL-5.(ABSTRACT TRUNCATED AT 250 WORDS)
Blood Rev 1989 Dec
PMID:Multifunctional cytokines in haemopoiesis. 269 46

The regulation of the synthesis of alpha-2-HS glycoprotein (AHSG) by inflammatory mediators from activated monocytes was studied on the human hepatoma cell line HepG2 and compared to that of albumin. Monocyte-conditioned medium, recombinant human interleukin-6 (rhIL6) and interleukin-1 beta (rhIL1 beta) all down-regulated the synthesis of AHSG. This decrease was found both at the protein and the mRNA level. The most efficient mediator was the monocyte-conditioned medium, when rhIL1 beta was found to be less efficient than rhIL6. The combination of rhIL6 and rhIL1 beta resulted in an additive down-regulation of the AHSG mRNA levels. Similar results were obtained with albumin. These data indicate that AHSG is a negative acute-phase protein whose synthesis is regulated by cytokines in a manner similar to that of albumin.
FEBS Lett 1988 Dec 05
PMID:The synthesis of human alpha-2-HS glycoprotein is down-regulated by cytokines in hepatoma HepG2 cells. 284 21

Immune responses result in a variety of metabolic adjustments that are mediated by cytokines of leukocytic origin. Of the dozens of cytokines released during an immune response, interleukin-1 (IL-1), tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) are the major mediators of intermediary metabolism. These three cytokines act in concert to decrease food intake, increase resting energy expenditure, gluconeogenesis, glucose oxidation, and hepatic synthesis of fatty acids and acute phase proteins, decrease fatty acid uptake by adipocytes and alter the distribution of zinc, iron and copper. Most of these activities result from direct interactions between the cytokine and the responding cells. IL-1, TNF alpha and IL-6 also affect changes in metabolism by changing levels of circulating insulin, glucagon and corticosterone. The nutritional impact of these metabolic changes is dependent upon age. In growing animals, increases in energy expenditure and oxidation of amino acids are balanced by lower needs associated with growth. In adult animals, energy and amino acid requirements are increased by an amount similar to the increased basal metabolic rate and amino acid oxidation. Nutrition also influences the release of cytokines and consequently affects regulation of the immune response. For example, protein deficiency results in decreased IL-1 release and impaired tissue responses to IL-1.
J Nutr 1988 Dec
PMID:Nutritional aspects of leukocytic cytokines. 306 44

The induction of cytotoxic T lymphocytes (CTL) from CTL precursors requires a combination of antigen and lymphokine signals. To investigate lymphokine requirements for CTL generation, we used an assay in which helper T cell and accessory cell-depleted spleen cells or whole thymocytes were cultured with lectin (Con A) and lymphokines. This culture was followed by assessment of lectin-dependent cytolysis. High concentrations of recombinant interleukin 2 (R-IL 2) (100 U/ml) alone were not sufficient for lectin-mediated CTL induction from thymocytes, whereas 20 to 100 U/ml of R-IL 2 alone could induce a significant lectin-mediated CTL response from accessory cell-depleted spleen cells. Using thymocytes as responders, we found purified or recombinant interferon-gamma (IFN-gamma) did not cause cytolytic activity either in the absence of or in the presence of R-IL 2. However, supernatant from Con A-stimulated rat spleen cells (rat Con A SN) in combination with R-IL 2 could induce cytolytic activity, suggesting that several factors are required for CTL induction. Con A SN was fractionated by gel filtration and the fractions were tested for ability to induce CTL. In the presence of a low level of R-IL 2 (5 U/ml), fractions with a Mr of approximately 31,000 could induce CTL, and this activity was referred to as CTL differentiation factor (CDF). The peak fractions containing CDF activity did not have detectable IL 1, IL 2, IFN-gamma, or CSF activity. However, by add-back experiments and the use of blocking antibodies, a monoclonal antibody against the IL 2 receptor or antibodies against murine IFN-gamma, we demonstrated that CTL induction from mature thymocytes (L3T4-, Lyt-2+) requires CDF activity in addition to IL 2 and IFN-gamma.
J Immunol 1986 Dec 01
PMID:Requirement for three distinct lymphokines for the induction of cytotoxic T lymphocytes from thymocytes. 309 23

Serial observations of blast cell colony development from spleen cells of mice treated with 5-fluorouracil (5-FU) four days earlier revealed that either form of human interleukin-1 (IL-1 alpha or IL-1 beta) hastens the emergence of interleukin-3 (IL-3)-dependent blast cell colonies. This activity was essentially indistinguishable from the effect of interleukin-6 (IL-6) or granulocyte colony-stimulating factor (G-CSF) in the same system, an effect that we have ascribed previously to a shortening of the G0 period of the dormant stem cells. We also analyzed the time courses of colony formation from cultures of day-2 post-5-FU marrow cells supported by IL-1 alpha, IL-6, or G-CSF alone or in combination with IL-3. In the presence of IL-3, G-CSF and IL-6 but not IL-1 alpha hastened the development of colonies and increased the numbers of multilineage colonies relative to cultures of IL-3 alone. This observation, together with our previous data from the human system, suggests that the synergistic effect of IL-1 is likely due to induction of secondary growth factors, including IL-6 and G-CSF, by accessory cells in culture. The effect of IL-6 on G0 was confirmed by analysis of the cycling status of progenitor cells in short-term culture. While neither IL-3 nor IL-6 alone had any effect on the cycling status, the combination of factors resulted in a rapid recruitment of quiescent cells into cell cycle (within 48 hours) as represented by a twofold increase in the numbers of multipotential progenitors and a significant increase in the sensitivity of these cells to 3H-thymidine with high specific activity. Combinational testing of all of these synergistic factors revealed that the target cell populations for the IL-1, IL-6, and G-CSF overlap considerably, suggesting that they all may act through a common mechanism. This is further supported by our finding that cells from blast cell colonies grown in the presence of a combination of any one of the synergistic factors with IL-3 replate with higher efficiency and yield more multilineage secondary colonies than those from colonies grown in IL-3 alone. These findings provide further evidence that IL-1, IL-6, and G-CSF serve to integrate the immediate host responses to infection through augmentation of effector cells and antibody production as well as the longer term host responses by recruitment of dormant hemopoietic stem cells into active cell cycling.
Blood 1988 Dec
PMID:Synergistic factors for stem cell proliferation: further studies of the target stem cells and the mechanism of stimulation by interleukin-1, interleukin-6, and granulocyte colony-stimulating factor. 326 95


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