A Nuclear Factor for the IL-6 Gene (NF-IL6)

Akira, Shizuo; Isshiki, Hiroshi; Nakajima, Takeshi; Kinoshita, Shigemi; Nishio, Yukihiro; Hashimoto, Shigeru; Natsuka, Shunji; Kishimoto, Tadamitsu

doi:10.1159/000319094

Cited by 31 publications

(24 citation statements)

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“…The antibody stained discrete two protein bands with molecular masses of 46 and 44 kDa; the 44 kDa band was stained much stronger by the antibody. These two proteins are considered to be derived from the first two AUGcodons of C/EBP/3 mRNA (1,60). The intensity of the two signals did not significantly change in HL-60 cells after VD3treatment (Fig.…”

Section: Expression Of Mrp14in Human Monocytic Leukemia Cellsmentioning

confidence: 95%

“…C/EBPa and -/3 are reported to recognize the same nucleotide sequence (1). Weidentified that the binding factor was C/EBP/3 in VD3-treated HL-60 cells, C/EBPa in human monocytic leukemia THP-1 cells, which constitutively expressed MRPproteins.…”

mentioning

confidence: 99%

“…C/EBP family is a basic leucine zipper transcriptional factor and has several members (1,6,10,26,41). C/EBPa and -/3 are reported to recognize the same nucleotide sequence (1).…”

mentioning

confidence: 99%

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Transcriptional Regulation by C/EBP.ALPHA. and -.BETA. in the Expression of the Gene for the MRP14 Myeloid Calcium Binding Protein.

Kuruto-Niwa

Nakamura

Takeishi

et al. 1998

Cell Struct. Funct.

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ABSTRACT.Transcriptional regulation of the gene for the myeloid calcium binding protein, MRP14, was investigated in humanmonocytic leukemia cell lines. The MRP14gene was not expressed in monoblastic ML-1 cells, promonocytic U-937 cells, or promyelocytic HL-60 cells. On the other hand, the gene was expressed in monocytic THP-1 cells and in the HL-60 cells treated with 1,25-dihydroxyvitamin D3 (VD3). The level of MRP14in VD3-treated HL-60 cells was two-fold higher than that in THP-1 cells. Amongseveral known transcription factor binding motifs, nuclear protein(s) of VD3-treated HL-60 cells and THP-1 cells bound to the CCAAT/enhancerbinding protein (C/EBP)-binding motif that was located in the upstream region of the MRP14gene (-81), as evidenced by the competitive gel mobility-shift assay. An antibody for C/EBPa supershifted the nucleoprotein complex in THP-1 cells but not in the VD3-treated HL-60 cells, whereas an antibody for C/EBP^blocked the formation of the complex with the nuclear factor of the HL-60 cells but not with that of THP-1 cells. An anti-C/EBPd antibody had no effect on the complex in either cell. Thus, it was concluded that C/EBPa and -fi were able to bind to the C/EBP motif, and that C/EBPa bound to the motif in THP-1 cells and C/EBP^bound to that in the VD3-treated HL-60 cells. Furthermore, to examine the transcriptional activity of the C/EBP motif, we transfected several constructed luciferase reporter DNAsinto HL-60 cells and THP-1 cells. The luciferase activity of the C/EBP motif in HL-60 cells was increased by VD3treatment. The C/EBP motif in the MRP14gene was confirmed to function as a regulatory region in VD3-treated HL-60 cells and THP-1 cells by the assay. Since C/EBP/9 was also detected in VD3-untreated HL-60 cells by immunoblotting, VD3 activated C/EBP/9 to bind to the motif, probably through post-translational modification.Myeloid calcium binding proteins, MRP8and MRP14 (25, 35), also designated cystic fibrosis antigen (5, 12), the leukocyte LI molecule (4), the 60B8 antigen (34, 55), p8/pl4 (17), calgranulin A/B (22), and calprotectin (51, 66), are members of the S100 protein family, whose genes are knownto be localized in the cluster on human chromosome Iq21 (46). Therefore, it has been proposed that MRP8and MRP14be called S100A8 and S100A9, respectively (46).

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Section: Expression Of Mrp14in Human Monocytic Leukemia Cellsmentioning

confidence: 95%

mentioning

confidence: 99%

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Transcriptional Regulation by C/EBP.ALPHA. and -.BETA. in the Expression of the Gene for the MRP14 Myeloid Calcium Binding Protein.

Kuruto-Niwa

Nakamura

Takeishi

et al. 1998

Cell Struct. Funct.

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“…The C/EBP␤ transcription factor is an important regulator of inflammation (18,19). C/EBP binding sites are present in many promoters of proinflammatory cytokines as well as in the HIV-1 LTR.…”

Section: Differentiation Of Monocytes To Macrophages Switches the Mycmentioning

confidence: 99%

Differentiation of Monocytes to Macrophages Switches theMycobacterium tuberculosisEffect on HIV-1 Replication from Stimulation to Inhibition: Modulation of Interferon Response and CCAAT/Enhancer Binding Protein β Expression

Weiden

Tanaka

Qiao³

et al. 2000

The Journal of Immunology

118

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HIV-1 replication is inhibited in uninflamed lung macrophages and is stimulated during tuberculosis. Attempts to recapitulate activation of HIV-1 replication in primary monocytes and macrophages ex vivo and in the untreated and PMA-treated THP-1 cell line model in vitro have produced opposite results depending on the state of differentiation of the cells. After infection with Mycobacterium tuberculosis, monocytes enhanced HIV-1 replication and produced a stimulatory 37-kDa CCAAT/enhancer binding protein β (C/EBPβ) transcription factor, whereas macrophages suppressed HIV-1 replication and produced an inhibitory 16-kDa C/EBPβ transcription factor. IFN-β induced inhibitory 16-kDa C/EBPβ in macrophages, but had no effect on C/EBPβ expression in monocytes. Macrophages, but not monocytes, were able to activate IFN-stimulated gene factor-3 (ISGF-3), a transcription factor composed of STAT-1, STAT-2, and IFN regulatory factor (IRF)-9, after infection with M. tuberculosis or stimulation with type I IFN. Macrophages expressed IRF-9 DNA-binding activity, but monocytes did not, and addition of the IRF-9 component reconstituted ISGF-3 in extracts of IFN-treated monocytes. Modulation of IFN responsiveness upon differentiation occurred at least in part through a post-transcriptionally regulated increase in IRF-9 expression. Both monocytes and macrophages maintained IFN responsiveness, activating STAT-1 homodimer formation and transcription of the STAT-1 gene after IFN stimulation. In addition, both monocytes and macrophages were able to activate NF-κB upon infection with M. tuberculosis. These results show that induction of ISGF-3, expression of the inhibitory 16-kDa C/EBPβ, and suppression of HIV-1 replication via a transcriptional mechanism are macrophage-specific responses to infection with M. tuberculosis.

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“…The C/EBPs bind to DNA exclusively as dimers and contain a conserved C-terminal basic region-leucine zipper domain that is characterized by a DNA-contacting basic region linked to a leucine zipper dimerization motif (18). They bind preferentially to a consensus DNA sequence T(T/G)NNGNAA(T/G) (19,20). The founding member of the family of C/EBP transcription factors, C/EBP␣, is expressed during terminal differentiation of cells such as adipocytes (13) and keratinocytes.…”

mentioning

confidence: 99%

Pancreatic β-Cell-specific Repression of Insulin Gene Transcription by CCAAT/Enhancer-binding Protein β

Lu¹,

Seufert²,

Habener

1997

Journal of Biological Chemistry

120

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Chronic exposure of ␤-cells to supraphysiologic glucose concentrations results in decreased insulin gene transcription. Here we identify the basic leucine zipper transcription factor, CCAAT/enhancer-binding protein ␤ (C/EBP␤), as a repressor of insulin gene transcription in conditions of supraphysiological glucose levels. C/EBP␤ is expressed in primary rat islets. Moreover, after exposure to high glucose concentrations the ␤-cell lines HIT-T15 and INS-1 express increased levels of C/ EBP␤. The rat insulin I gene promoter contains a consensus binding motif for C/EBP␤ (CEB box) that binds C/EBP␤. In non-␤-cells C/EBP␤ stimulates the activity of the rat insulin I gene promoter through the CEB box. Paradoxically, in ␤-cells C/EBP␤ inhibits transcription, directed by the promoter of the rat insulin I gene by direct protein-protein interaction with a heptad leucine repeat sequence within activation domain 2 of the basic helix-loop-helix transcription factor E47. This interaction leads to the inhibition of both dimerization and DNA binding of E47 to the E-elements of the insulin promoter, thereby reducing functionally the transactivation potential of E47 on insulin gene transcription. We suggest that the induction of C/EBP␤ in pancreatic ␤-cells by chronically elevated glucose levels may contribute to the impaired insulin secretion in severe type II diabetes mellitus.Insulin is a hormone essential for the control of mammalian glucose homeostasis and is produced predominantly in pancreatic ␤-cells of adult animals (1). The expression of the insulin gene occurs to a large extent at the level of transcription. Control elements residing in the 5Ј 350-base pair sequence flanking exon 1 of the rat insulin I gene are sufficient to direct ␤-cell-specific expression (2) (Fig. 1A). Arrays of A and E elements 1 (Far-FLAT, Nir-P1) constitute symmetrical enhansons that cooperatively account for Ͼ90% of the transcriptional activity of the insulin gene promoter (3). The E elements are recognition motifs for transcription factors in the basic helixloop-helix (bHLH) 2 family, such as E12 and E47, which activate the insulin promoter in close synergism with A element binding homeobox transcription factors, such as IDX-1.Chronic hyperglycemia may contribute to the pancreatic ␤-cell dysfunction observed in patients with type II diabetes, a phenomenon attributed to the concept of glucose toxicity (4). Studies using in vivo animal models and in vitro ␤-cell lines have demonstrated that a reduction of insulin gene transcription by glucose toxicity is associated with the loss of transactivator proteins such as IDX-1/IPF-1/STF-1 and RIPE3b1-binding protein (5-10). Because insulin gene transcription is both positively and negatively regulated, we sought to identify repressors that might also mediate the effects of glucose toxicity on insulin gene transcription. In this report we describe CCAAT/enhancer binding protein-␤ (C/EBP␤) as a glucoseinduced repressor of insulin gene transcription.C/EBPs are a family of transcription factors that regulate...

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A Nuclear Factor for the IL-6 Gene (NF-IL6)

Cited by 31 publications

References 0 publications

Transcriptional Regulation by C/EBP.ALPHA. and -.BETA. in the Expression of the Gene for the MRP14 Myeloid Calcium Binding Protein.

Transcriptional Regulation by C/EBP.ALPHA. and -.BETA. in the Expression of the Gene for the MRP14 Myeloid Calcium Binding Protein.

Differentiation of Monocytes to Macrophages Switches theMycobacterium tuberculosisEffect on HIV-1 Replication from Stimulation to Inhibition: Modulation of Interferon Response and CCAAT/Enhancer Binding Protein β Expression

Pancreatic β-Cell-specific Repression of Insulin Gene Transcription by CCAAT/Enhancer-binding Protein β

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