Lymphoproliferative disorder and imbalanced T-helper response in C/EBP beta-deficient mice.

Screpanti, Isabella; Romani, Luigina; Musiani, Piero; Modesti, Andrea; Fattori, Elena; Lazzaro, Domenico; Sellitto, Carolina; Scarpa, Susanna; Bellavia, Diana; Lattanzio, Giuseppe

doi:10.1002/j.1460-2075.1995.tb07185.x

Cited by 383 publications

(370 citation statements)

References 35 publications

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“…C/EBP␤ is a member of the leucine zipper family of CCAAT enhancerbinding proteins. All members of this family are important regulators of gene expression, particularly involved in inflammatory response and energy metabolism (44,36). C/EBP␤ is present in the majority of cells in two main isoforms.…”

Section: Discussionmentioning

confidence: 99%

Differences in regulation of type I collagen synthesis in primary and passaged hepatic stellate cell cultures: the role of α₅β₁-integrin

Dodig¹,

Ogunwale²,

Dasarathy³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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Hepatic stellate cells (HSC) differ in their phenotype depending on the initiation and progression of their activation. Our hypothesis was that different mechanisms govern type I collagen synthesis depending on stage of HSC activation. We investigated the role of ␣5␤1-integrin as a regulator of type I collagen gene COL1A1 expression in primary and passaged HSC cultures using transgenic mouse containing type I collagen gene COL1A1 promoter linked to the chloramphenicol acetyltransferase (CAT) reporter gene. The ␣5␤1 protein levels increased during the activation and were highest in day 6 primary cultures but decreased in passaged HSC. CAT activity, reflecting COL1A1 expression, was upregulated by ␣5␤1-integrin. Inhibition of ␣5␤1-integrin by echistatin and blocking antibody resulted in reduced transgene activity only in early primary cultures (compared with the control, 53.3 Ϯ 12% echistatin and 58.8 Ϯ 7% blocking antibody, respectively, P Ͻ 0.05). Treatment of passaged HSC with either echistatin or blocking antibody had no effect. Fibronectin, an ␣5␤1-integrin ligand, increased transgene activity in primary (210 Ϯ 33%, P Ͻ 0.05) but not in passaged HSC cultures (119 Ϯ 8%). This ␣5␤1-integrin effect appears to be at least in part mediated by CCAAT enhancer binding protein-␤ (C/EBP␤), because fibronectin increased and ␣5-gene silencing by small interfering RNA decreased C/EBP␤ levels. In addition, C/EBP␤ knockout mice showed reduced type I collagen synthesis compared with wild-type littermates. Therefore ␣5␤1-integrin is an important regulator of type I collagen production in early primary HSC cultures but appears to have no direct role once the HSC are fully activated.

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Section: Discussionmentioning

confidence: 99%

Differences in regulation of type I collagen synthesis in primary and passaged hepatic stellate cell cultures: the role of α₅β₁-integrin

Dodig¹,

Ogunwale²,

Dasarathy³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…The TNF-␣ promoter, like the HIV-1 LTR, is strongly repressed by engineered expression of the inhibitory C/EBP␤ in monocytes (68). C/EBP␤ knockout mice, but not mice deficient in both IL-6 and C/EBP␤, develop a lymphoproliferative disease associated with high levels of IL-6 (69,70), suggesting that C/EBP␤ is an important negative regulator of IL-6 production in vivo. Finally, aerosolized IFN-␣ inhibits IL-6 and TNF-␣ production in the lungs of patients with tuberculosis (71).…”

Section: Discussionmentioning

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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“…For example, two groups have reported the targeted disruption of the c/ebp␤ gene (51,52) and have shown that this mutation has only minor effects on the expression of inflammatory cytokine genes. These results are surprising in light of previous data showing that C/EBP␤ plays a critical role in the expression of genes such as interleukin-1, interleukin-6, and monocyte chemoattractant protein-1 in cell lines (26,(53)(54)(55), and suggest that a redundant C/EBP activity compensates for the absence of C/EBP␤ in knockout animals.…”

Section: Discussionmentioning

confidence: 99%

Design of a C/EBP-specific, Dominant-negative bZIP Protein with Both Inhibitory and Gain-of-function Properties

Olive

Williams

Dezan

et al. 1996

Journal of Biological Chemistry

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We have developed a bZIP protein, GBF-F, with both dominant-negative (DN) and gain-of-function properties. GBF-F is a chimera consisting of two components: the DNA binding (basic) region from the plant bZIP protein GBF-1 (GBF) and a leucine zipper (F) designed to preferentially heterodimerize with the C/EBP␣ leucine zipper. Biochemical studies show that GBF-F preferentially forms heterodimers with C/EBP␣ and thus binds a chimeric DNA sequence composed of the half-sites recognized by the C/EBP and GBF basic regions. Transient transfections in HepG2 hepatoma cells show that both components of GBF-F are necessary for inhibition of C/EBP␣ transactivation. When the C/EBP␣ leucine zipper is replaced with that of either GCN4 or VBP, the resulting protein can transactivate a C/EBP cis-element but is not inhibited by GBF-F, indicating that the specificity of dominant-negative action is determined by the leucine zipper. All known members of the C/EBP family contain similar leucine zipper regions and are inhibited by GBF-F. GBF-F also exhibits gain-of-function properties, since, with the essential cooperation of a C/EBP family member, it can transactivate a promoter containing the chimeric C/EBPͦGBF site. This protein therefore has potential utility both as a dominant-negative inhibitor of C/EBP function and as an activator protein with novel DNA sequence specificity.

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Lymphoproliferative disorder and imbalanced T-helper response in C/EBP beta-deficient mice.

Cited by 383 publications

References 35 publications

Differences in regulation of type I collagen synthesis in primary and passaged hepatic stellate cell cultures: the role of α₅β₁-integrin

Differences in regulation of type I collagen synthesis in primary and passaged hepatic stellate cell cultures: the role of α₅β₁-integrin

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

Design of a C/EBP-specific, Dominant-negative bZIP Protein with Both Inhibitory and Gain-of-function Properties

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Lymphoproliferative disorder and imbalanced T-helper response in C/EBP beta-deficient mice.

Cited by 383 publications

References 35 publications

Differences in regulation of type I collagen synthesis in primary and passaged hepatic stellate cell cultures: the role of α5β1-integrin

Differences in regulation of type I collagen synthesis in primary and passaged hepatic stellate cell cultures: the role of α5β1-integrin

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

Design of a C/EBP-specific, Dominant-negative bZIP Protein with Both Inhibitory and Gain-of-function Properties

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Product

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Differences in regulation of type I collagen synthesis in primary and passaged hepatic stellate cell cultures: the role of α₅β₁-integrin

Differences in regulation of type I collagen synthesis in primary and passaged hepatic stellate cell cultures: the role of α₅β₁-integrin