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)

The secretion of alpha 1-microglobulin by primary cultures of rat hepatocytes was found to increase upon the addition of interleukin-6 or leukemia inhibitory factor, two mediators of acute phase response. This stimulatory effect was further enhanced by dexamethasone. alpha 1-Microglobulin is synthesized as a precursor also containing bikunin, and the precursor protein is cleaved shortly before secretion. Our results therefore suggest that both alpha 1-microglobulin and bikunin are acute phase reactants in rat hepatocytes. Furthermore, we found that retinoic acid, previously shown to be involved in the regulation of cell differentiation and development, also stimulated alpha 1-microglobulin synthesis. Only free, uncomplexed alpha 1-microglobulin (28,000 Da) was detected in the hepatocyte media, suggesting that the complex between alpha 1-microglobulin and alpha 1-inhibitor 3, found in rat serum, is formed outside the hepatocyte.
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PMID:Synthesis of alpha 1-microglobulin in cultured rat hepatocytes is stimulated by interleukin-6, leukemia inhibitory factor, dexamethasone and retinoic acid. 137 72

We established a radiation-induced murine hematopoietic cell line, Y6, that could be induced to differentiate into macrophages by interleukin-6 (IL-6). IL-6 also induced growth inhibition and apoptosis in Y6 cells. Retinoic acid (RA) inhibited such effects of IL-6 on Y6 cells. The inhibitory effect of RA on the effects of IL-6 was not caused by the downregulation of the IL-6 receptor, because RA neither affected the expression of IL-6 receptor mRNA nor the expression of IL-6 receptor molecule on the cell surface. Furthermore, RA did not inhibit the IL-6-induced expression of junB mRNA, indicating that the expression of functionally active IL-6 receptor and the signal transduction pathway activating the junB gene are not inhibited by RA. IL-6-induced macrophage differentiation of Y6 cells was preceded by the downregulation of the c-myc gene, which was also prevented by RA. Because the inhibitory effect of RA on Y6 cells was reversible and seemed not to require de novo protein synthesis, the RA receptor by itself might be directly involved in the inhibition of the IL-6 signal transduction pathway. The results indicated that the IL-6 signal transduction pathways leading to the induction of macrophage differentiation and junB gene expression can be dissected by RA.
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PMID:Retinoic acid inhibits interleukin-6-induced macrophage differentiation and apoptosis in a murine hematopoietic cell line, Y6. 138

Two cell clones [BE(2)-C and BE(2)-M17] derived from the human neuroblastoma cell line SK-N-BE(2) express corticotrophin-releasing hormone as well as interleukin-6 mRNA. Both genes are overexpressed, although with a different time course, following exposure to 5 microM retinoic acid, in parallel to the induction of neuroblastic differentiation. On the contrary, we are unable to detect interleukin-1 beta mRNA in these cell lines. Both cytokines are known to increase hypothalamic CRH mRNA. The production of cytokines and neuropeptides by neuroblastoma cells indicate a complex dialogue between tumour cells and anti-tumour immunity.
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PMID:Interleukin-6 and corticotrophin-releasing hormone mRNA are modulated during differentiation of human neuroblastoma cells. 140 16

PL-21 is a promyelocytic leukemia cell line that produces plasminogen activator inhibitor 2 (PAI-2). Differentiation-linked expression of PAI-2 was investigated by adding cell-differentiation promoting agents [such as phorbol myristate acetate (PMA), retinoic acid (RA), dexamethasone (Dex), and recombinant cytokines, including tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), granulocyte-colony stimulating factor (G-CSF), and interleukin-6 (IL-6)] into the culture medium of PL-21 cells. PAI-1 and PAI-2 antigens were measured by an enzyme-linked immunoassay. The PAI-1 antigen, however, became detectable only after stimulation. The presence of PAI-2 antigen was further verified by immunoblotting using a monoclonal antibody against PAI-2 purified from a PL-21 culture medium. PAI activity both in the culture medium and in the cell lysate increased approximately 70-fold after exposure to PMA. Both PAI-1 and PAI-2 antigens increased, but the amount of the latter in the culture medium and in the cell lysate was approximately 10 times and 2,500 times, as much, respectively, as that of the former. Dex also increased the intracellular PAI activity approximately 6-fold, parallel with PAI-2 antigen. PAI-1 antigen increased only slightly in the culture medium but not in the cell lysate after Dex-stimulation. As with the case of PMA, TNF-alpha and IL-6 induced PL-21 cells to macrophage-like cells, but did not affect the PAI activity. Thus, the increase of the PAI-2 production by PMA may not necessarily depend on differentiation into macrophages. Other cytokines examined did not increase the PAI activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dexamethasone and phorbol ester, but not cytokines, increase the production of plasminogen activator inhibitor type-2 in the PL-21 human promyelocytic leukemia cell line. 177 17

1. The effect of recombinant human interleukin-6 on the antiproliferation and differentiation inducing actions of all-trans retinoic acid in HL-60 human myeloid leukaemia cells was studied in short-term liquid suspension culture. 2. Interleukin-6 alone showed no significant effect on HL-60 human myeloid leukaemia cells. 3. The addition of interleukin-6 to all-trans retinoic acid-treated cultures of HL-60 human myeloid leukaemia cells significantly enhanced the desired antiproliferation effect of all-trans retinoic acid. 4. The combination of interleukin-6 with all-trans retinoic acid reduced the doses of all-trans retinoic acid required to induce the same differentiation of HL-60 cells as single agent by between 1.7- and 4.8-fold; that is, the efficacy of all-trans retinoic acid in inducing the differentiation of human myeloid leukaemia HL-60 cells was increased up to 4.8 times by its combination with interleukin-6. 5. The combination of all-trans retinoic acid and interleukin-6 could provide an effective alternative therapy for elderly myeloid leukaemia patients.
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PMID:Recombinant human interleukin-6 enhances the antiproliferation and differentiation inducing effects of retinoic acid in HL-60 human myeloid leukaemic cells. 179 49

Differentiation-linked expression of plasminogen activator inhibitor-2 (PAI-2) was investigated by adding cell-differentiation promoting agents [such as phorbol myristate acetate (PMA), retinoic acid, dexamethasone (Dex), and recombinant cytokines, including tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta, granulocyte-colony stimulating factor, and interleukin-6 (IL-6)] into the culture medium of a promyelocytic leukemia cell line PL-21. PAI activity both in the culture medium and in the cell lysate increased approximately 70-fold after exposure to PMA. Both PAI-1 and PAI-2 antigens increased, but the amounts of the latter in the culture medium and in the cell lysate were approximately 10 times and 2,500 times, as much, respectively, as those of the former. Dex also increased the intracellular PAI activity approximately 6-fold, parallel with PAI-2 antigen. PAI-1 antigen increased only slightly in the culture medium but not in the cell lysate after Dex-stimulation. As with the case of PMA, TNF-alpha and IL-6 induced PL-21 cells to macrophage-like cells, but did not affect the PAI activity. Thus, the increase of the PAI-2 production by PMA may not necessarily depend on differentiation into macrophages. Other cytokines examined did not increase the PAI activity. PAI-2 antigen was demonstrated in the cell lysates of various leukemia cells by Western blotting technique using a monoclonal antibody against the PAI-2 purified from PL-21 culture medium. PAI-2 antigen was frequently detected in the plasmas from the patients whose peripheral leukocytes were more than 10,000/microliters.
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PMID:[Production and secretion of the plasminogen activator inhibitor type-2 in a leukemia cell line]. 187 Feb 66

This study examines the effect of leukemia inhibitory factor (LIF) on preosteoblastic rat calvaria (RCT-1) cells, which acquire osteoblastic properties when treated with retinoic acid (RA). LIF potentiated the increase in alkaline phosphatase (AP) activity produced by RA. The LIF effect was time and dose dependent (EC50, approximately 1 pM). The earliest effects on AP activity were detected at 48 h, and maximal effects were observed after 72 h. RA increased AP mRNA about 2-fold at 3 h and 6-fold at 6 and 12 h. LIF further increased AP mRNA to 18-fold at 12 h. After RA treatment AP mRNA returned to control levels at 24 h, but in the presence of LIF, AP mRNA remained elevated at 24 and 72 h of treatment. When given alone, LIF had no effect on either AP activity or mRNA levels. Tumor necrosis factor-alpha and 1,25-dihydroxyvitamin D3 also potentiated the RA induction of AP, and interleukin-6 had a small effect, whereas granulocyte macrophage colony-stimulating factor had no effect. LIF alone had a small inhibitory effect on type 1 collagen mRNA, but did not oppose the stimulatory effect of RA. Consistent with these biological actions, LIF receptors were demonstrated on these cells. [125I]LIF bound to RCT-1 cells at 0 C with an apparent dissociation constant of 20 pM, and it was found that these cells express an average of 300 receptors/cell. Scatchard analyses showed a single class of high affinity binding site. LIF was internalized with an endocytic rate constant for occupied receptors of 0.03 min-1, and the apparent equilibrium dissociation constant at 37 C was 358 pM. These findings suggest that osteoblast precursor cells are among the target cells of LIF.
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PMID:Leukemia inhibitory factor binds with high affinity to preosteoblastic RCT-1 cells and potentiates the retinoic acid induction of alkaline phosphatase. 211 91

Rat hepatoma cells H-35 cultured in serum-free medium were exposed to interleukin-6 (IL-6), interleukin-1 (IL-1), hepatocyte growth factor (HGF), retinoic acid (RA), or a mixture of these factors. Production of acute phase proteins, responding to IL-6 alone (type 2) or to the mixture of IL-6 and IL-1, was assessed by electroimmunoassay and the corresponding mRNAs were compared by Northern blot analysis. HGF enhanced IL-6-induced synthesis of alpha-2-macroglobulin but reduced synthesis of C3 complement and alpha-1-acid glycoprotein. Retinoic acid reduced the response to IL-6 of alpha-2-macroglobulin but enhanced that of alpha-1-acid glycoprotein and especially of C3 complement. In general, changes in protein secretion were correlated with the contents of their corresponding cellular mRNAs. These results indicate that hepatocyte growth factor can enhance basal or IL-6-induced gene expression of type 2 and reduce the expression of type 1 acute phase proteins, whereas the action of retinoic acid is opposite. The modulation of acute phase response by HGF and RA likely involves transcriptional factors and regulatory sequences in the genes coding for these two types of acute phase proteins.
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PMID:Hepatocyte growth factor and retinoic acid exert opposite effects on synthesis of type 1 and type 2 acute phase proteins in rat hepatoma cells. 753 94

Human cytosolic aldehyde dehydrogenase 1 (ALDH1) plays a role in the biosynthesis of retinoic acid that is a modulator for gene expression and cell differentiation. Northern blot analysis showed that liver tissue, pancreas tissue, hepatoma cells, and genital skin fibroblast cells expressed high levels of ALDH1. Sequence analysis showed that the 5'-flanking region contains a number of putative regulatory elements, such as NF-IL6, HNF-5, GATA binding sites, and putative response elements for interleukin-6, phenobarbital and androgen, in addition to a noncanonical TATA box (ATAAA) and a CCAAT box. Functional characterization of the 5'-regulatory region of the human ALDH1 gene was carried out by a fusion to the chloramphenicol acetyltransferase gene. A construct containing 2.6 kilobase pairs of the 5'-flanking region was efficiently expressed in hepatoma Hep3B cells, but not in erythroleukemic K562 cells or in fibroblast LTK- cells, which do not express ALDH1. Within this region, we define a minimal promoter (-91 to +53) that contains positive regulatory elements. The study using site-directed mutagenesis demonstrated that the CCAAT box region is the major cis-acting element involved in basal ALDH1 promoter activity in Hep3B cells. Gel mobility shift assays showed that NF-Y and other octamer factors bound CCAAT box and an octamer motif sequence, but not GATA site existing in the minimal promoter region. Two additional DNA binding activities associated with the minimal promoter were found in the nuclear extract from Hep3B cells, but not from K562 cells. These results offer the possible molecular mechanism of the cell type-specific expression of ALDH1 gene.
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PMID:The transcriptional regulation of human aldehyde dehydrogenase I gene. The structural and functional analysis of the promoter. 761 57

HepG2 cells were cultured for 7 days in serum-free medium in the presence of interleukin-6 (IL-6), retinoic acid (RA) or dexamethasone (DX), and some plasma proteins secreted to the media were determined by electroimmunoassay whereas the contents of specific mRNAs in the cells was evaluated by Northern blot hybridization. Interleukin-6 maximally stimulated synthesis of alpha-1-antichymotrypsin between days 1 and 3 whereas the response of fibrinogen was delayed to days 3 to 7. Retinoic acid increased the effect of IL-6 on alpha-1-antichymotrypsin (ACT) and fibrinogen (FBG) on the level of both proteins and mRNAs. Synthesis of albumin was slightly inhibited by IL-6 and RA, and synthesis of transferrin was increased by RA but not by IL-6. Dexamethasone had small enhancing effect on the action of IL-6. These results suggest that long-term HepG2 cultures may provide an experimental model for liver acute phase response during chronic inflammation.
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PMID:Long-term culture of HepG2 hepatoma cells as a model for liver acute phase response during chronic inflammation. Effects of interleukin-6, dexamethasone and retinoic acid. 769 40


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