Heterogeneity of Hematopoietic Cells Immortalized by v-myc/v-raf Recombinant Retrovirus Infection of Bone Marrow or Fetal Liver

Cox, George W.; Mathieson, Bonnie J.; Gandino, Lucia; Blasi, Elisabetta; Radzioch, Danuta; Varesio, Luigi

doi:10.1093/jnci/81.19.1492

Cited by 118 publications

(77 citation statements)

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“…Several cell lines were established from ICSBP Ϫ/Ϫ bone marrow cells following transformation with the J2 retrovirus (30). Among them, a clone designated CL-2 expressed Mac-1 (CD11b), but not GR-1 (Ly-6G), a feature shared with macrophages in vivo ( …”

Section: Icsbp ϫ/ϫ Macrophage-like Cells Fail To Induce Il-12 P40 Tramentioning

confidence: 99%

An IFN-γ-Inducible Transcription Factor, IFN Consensus Sequence Binding Protein (ICSBP), Stimulates IL-12 p40 Expression in Macrophages

Wang

Contursi

Masumi

et al. 2000

The Journal of Immunology

172

177

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IL-12 is a cytokine that links innate and adaptive immunity. Its subunit p40 is induced in macrophages following IFN-γ/LPS stimulation. Here we studied the role for IFN consensus sequence binding protein (ICSBP), an IFN-γ/LPS-inducible transcription factor of the IFN regulatory factor (IRF) family in IL-12 p40 transcription. Macrophage-like cells established from ICSBP−/− mice did not induce IL-12 p40 transcripts, nor stimulated IL-12 p40 promoter activity after IFN-γ/LPS stimulation, although induction of other inducible genes was normal in these cells. Transfection of ICSBP led to a marked induction of both human and mouse IL-12 p40 promoter activities in ICSBP+/+ and ICSBP−/− cells, even in the absence of IFN-γ/LPS stimulation. Whereas IRF-1 alone was without effect, synergistic enhancement of promoter activity was observed following cotransfection of ICSBP and IRF-1. Deletion analysis of the human promoter indicated that the Ets site, known to be important for activation by IFN-γ/LPS, also plays a role in the ICSBP activation of IL-12 p40. A DNA affinity binding assay revealed that endogenous ICSBP is recruited to the Ets site through protein-protein interaction. Last, transfection of ISCBP alone led to induction of the endogenous IL-12 p40 mRNA in the absence of IFN-γ and LPS. Taken together, our results show that ICSBP induced by IFN-γ/LPS, acts as a principal activator of IL-12p40 transcription in macrophages.

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Section: Icsbp ϫ/ϫ Macrophage-like Cells Fail To Induce Il-12 P40 Tramentioning

confidence: 99%

An IFN-γ-Inducible Transcription Factor, IFN Consensus Sequence Binding Protein (ICSBP), Stimulates IL-12 p40 Expression in Macrophages

Wang

Contursi

Masumi

et al. 2000

The Journal of Immunology

172

177

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“…Forebears of TLR4ko mice and the wild-type littermates mice were a gift from K. Takeda and S. Akira (Osaka University, Osaka, Japan) (6). Bone marrow-derived transformed macrophage cell lines were derived as described (21,22). Macrophage cell lines and primary macrophages were cultured in DMEM with 4.5 g/L glucose (Invitrogen Life Technologies) supplemented with 10% heat inactivated FBS (endotoxin free; HyClone), 2 mM L-glutamine, 1 mM pyruvate, 200 U/ml penicillin, and 200 g/ml streptomycin in 7.5% CO 2 /92.5% air at 37°C.…”

Section: Cell Linesmentioning

confidence: 99%

Abrupt Expression of TLR4 in TLR4-Deficient Macrophages Imposes a Selective Disadvantage: Genetic Evidence for TLR4-Dependent Responses to Endogenous, Nonmicrobial Stimuli

Cohn

Nathan²,

Radzioch

et al. 2006

The Journal of Immunology

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TLR4 is crucial for macrophage responses to LPS. It is less clear whether TLR4 may also transduce signals from host factors, and if so, with what consequences. Immortalized bone marrow-derived macrophage cell lines, termed T4Cr and T4ko, were established from TLR4null strains, C57BL/10ScNCr and TLR4 knockout mice, respectively. Multiple transfections and selections were conducted to stably introduce TLR4 into these cell lines. Among 196 individual clones isolated, 48 expressed TLR4 on the cell surface but did not respond to LPS due to a deletion in the MyD88 gene. The remaining clones integrated TLR4 DNA into the genome but expressed neither detectable TLR4 mRNA nor TLR4 protein. To test the possibility that TLR4null cells lack modulating factors to protect against a harmful effect of TLR4, 15 stably transfected clones were generated in the presence of conditioned media from wild-type macrophages. Some of these cells expressed a small amount of TLR4 and regained responsiveness to LPS. Because no microbial ligands were available to the cell lines during their generation, signaling via endogenous ligands is likely to have occurred in TLR4-expressing, signal-competent macrophages and imposed a proliferative or other selective disadvantage. These studies support the existence of constitutive signaling via TLR4 during in vitro culture of macrophages without microbial products, and help account for the lack of reports of restoration of TLR4 expression in normally TLR4-expressing types of cells in vitro whose TLR4 genes are deleted or disrupted.

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“…31 It is possible that threshold amounts of IFNg driven by the Tk minimal promoter are responsible for this effect. Low constitutive IFNg production could also account for the increase in 2 0 -5 0 OAse with time in culture (Figure 3b).…”

Section: Activation Of Macrophage Vectors S Pastorino Et Almentioning

confidence: 99%

“…31 ANA-1 Mf were cultured in Activation of macrophage vectors S Pastorino et al Dulbecco's modified Eagle's medium (ICN Biomedicals, Aurora, OH, USA), supplemented with 10% heatinactivated fetal bovine serum (Hyclone Laboratories, Logan, UT, USA), 2 mM L-glutamine, 100 U/ml of penicillin and 100 mg/ml of streptomycin (Celbio, Milan, Italy).…”

Section: Cell Culturementioning

confidence: 99%

Picolinic acid- or desferrioxamine-inducible autocrine activation of macrophages engineered to produce IFNγ: an approach for gene therapy

et al. 2004

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Macrophage (Mf)-based vectors are highly mobile cellular shuttles designed to deliver therapeutic genes within the tissues. We engineered a mouse Mf cell line to express the murine interferon-g (IFNg) under the control of an inducible promoter containing the hypoxia-responsive element, which can be triggered by hypoxia and other stimuli. We show that this Mf vector can be induced to produce IFNg under normoxic conditions by stimulation with picolinic acid (PA), a catabolite of tryptophan, or desferrioxamine (DFX), an ironchelating drug. The Mf vector responds to IFNg with the induction of IRF-1 and of other IFNg-inducible genes, the expression of Ia antigens and induction of phagocytic activity.Inducible nitric oxygen synthase gene expression, nitric oxide production, as well as TNFa secretion were enhanced by PA or DFX as the sole stimuli. None of the above responses could be triggered individually by PA or DFX in control, normal Mf, indicating that the Mf vector overcame the need for costimulatory molecules derived from the immune system for its full activation. Furthermore, we demonstrate that extracellular iron can downregulate such response, thereby identifying an additional tool for the fine tuning of the Mf vector response to stimulation.

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Heterogeneity of Hematopoietic Cells Immortalized by v-myc/v-raf Recombinant Retrovirus Infection of Bone Marrow or Fetal Liver

Cited by 118 publications

References 0 publications

An IFN-γ-Inducible Transcription Factor, IFN Consensus Sequence Binding Protein (ICSBP), Stimulates IL-12 p40 Expression in Macrophages

An IFN-γ-Inducible Transcription Factor, IFN Consensus Sequence Binding Protein (ICSBP), Stimulates IL-12 p40 Expression in Macrophages

Abrupt Expression of TLR4 in TLR4-Deficient Macrophages Imposes a Selective Disadvantage: Genetic Evidence for TLR4-Dependent Responses to Endogenous, Nonmicrobial Stimuli

Picolinic acid- or desferrioxamine-inducible autocrine activation of macrophages engineered to produce IFNγ: an approach for gene therapy

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