Mouse macrophage clones immortalized by retroviruses are functionally heterogeneous.

Pirami, L.; Stockinger, Brigitta; Corradin, Sally Betz; Sironi, Marina; Sassano, Marica; Valsasnini, P.; Righi, Marco; Ricciardi‐Castagnoli, Paola

doi:10.1073/pnas.88.17.7543

Cited by 34 publications

(24 citation statements)

References 28 publications

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“…MHC class II expression was constitutive in the wild-type cells and could be slightly further induced by IFN-␥ treatment. In contrast, it was barely detectable in the untreated C/EBP␤ Ϫ/Ϫ cell lines where it could be strongly induced by IFN-␥, similarly to what was previously reported for VN-11-immortalized macrophages (39). The revertant r Ϫ/Ϫ cells displayed an intermediate phenotype, with appreciable MHC class II expression in basal conditions and induced levels comparable to those of both Ϫ/Ϫ and ϩ/ϩ cells.…”

Section: Characterization Of the C/ebp␤mentioning

confidence: 55%

C/EBPβGene Inactivation Causes Both Impaired and Enhanced Gene Expression and Inverse Regulation of IL-12 p40 and p35 mRNAs in Macrophages

Gorgoni

Maritano

Marthyn

et al. 2002

The Journal of Immunology

105

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The transcription factor C/EBPβ is believed to play a fundamental role in regulating activated macrophage functions. However, the molecular mechanisms and the target genes involved have been, so far, poorly characterized, partly due to the difficulty of reproducibly obtaining homogeneous and abundant primary macrophage populations. In this study, we describe the generation and characterization of immortalized macrophage-like cell lines from C/EBPβ-deficient and wild-type mice. Using these cells, we were able to identify a number of genes involved in activated macrophage functions whose induction was affected in the C/EBPβ−/− cells. IFN-γ/LPS-dependent induction of IL-6, IL-1β, TNF-α, inducible NO synthase, and plasminogen activator inhibitor-1 mRNAs was variably impaired, while IL-12 p40, RANTES and macrophage inflammatory protein-1β mRNAs were up-regulated in the absence of C/EBPβ. The differential mRNA expression correlated with differential transcription levels of the corresponding genes, and was in most cases confirmed in primary macrophage populations. Moreover, in sharp contrast to the enhanced induction of IL-12 p40 mRNA, C/EBPβ−/− primary macrophages derived from both the bone marrow and the peritoneal cavity displayed totally defective expression of IL-12 p35 mRNA. Therefore, the IL-12 p35 gene represents a novel obligatory target for C/EBPβ in macrophages and this may explain the defective production of bioactive IL-12 and the impaired Th1 responses of C/EBPβ-deficient mice to Candida albicans infection observed in previous work.

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Section: Characterization Of the C/ebp␤mentioning

confidence: 55%

C/EBPβGene Inactivation Causes Both Impaired and Enhanced Gene Expression and Inverse Regulation of IL-12 p40 and p35 mRNAs in Macrophages

Gorgoni

Maritano

Marthyn

et al. 2002

The Journal of Immunology

105

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“…These transformed cells exhibit a higher growth rate and saturation density, accompanied by an ability to grow in semisolid medium (Ramsay et al, 1990). When vmyc is overexpressed in bone marrow cells or early hematopoietic precursor cells, cell lines are established at varying stages of myelomonocytic di erentiation ranging from myeloblasts to monocytes (Chisholm et al, 1992;Pirami et al, 1991) which readily form tumors in syngeneic mice (Chisholm et al, 1992).…”

Section: V-myc and Cell Transformationmentioning

confidence: 99%

The v-myc oncogene

Lee

Reddy

1999

Oncogene

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“…Each line was derived from a mouse thymus infected with the VN-11 retrovirus, which bears an mycenv fusion thought to immortalize macrophages via autocrine macrophage colony-stimulating factor expression (55,56). As previously reported, the Lps n cell line (MT2) has cell-surface markers and functional characteristics of a macrophage (57,58). We characterized the expression of a panel of relevant cell-surface proteins by the Lps d (MTC) cell line; BMMO and RAW 264.7 and Lps n (MT2) macrophage lines were analyzed in parallel for comparison (Table I).…”

Section: Ref 15)mentioning

confidence: 99%

Role of Ceramide in Lipopolysaccharide (LPS)-induced Signaling

MacKichan

DeFranco

1999

Journal of Biological Chemistry

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Ceramide and ceramide-activated enzymes have been implicated in responses to bacterial lipopolysaccharide (LPS) and the proinflammatory cytokines tumor necrosis factor-␣ (TNF) and interleukin-1␤ (IL-1). Although TNF and IL-1 cause elevation of cellular ceramide, which is thought to act as a second messenger, LPS has been proposed to signal by virtue of structural similarity to ceramide. We have investigated the relationship between ceramide and LPS by comparing the effects of a cell-permeable ceramide analog (C 2 -ceramide) and LPS on murine macrophage cell lines and by measuring ceramide levels in macrophages exposed to LPS. We found that while both C 2 -ceramide and LPS activated c-Jun N-terminal kinase (JNK), only LPS also activated extracellular signal-regulated kinases (ERKs). C 2 -ceramide was also unable to activate NF-B, a transcription factor important for LPS-induced gene expression. Upon measurement of cellular ceramide in macrophage lines, we observed a small but rapid rise in ceramide, similar to that seen upon IL-1 or TNF treatment, suggesting LPS induces an increase in ceramide rather than interacting directly with ceramide-responsive enzymes. We found that C 2 -ceramide activated JNK and induced growth arrest in macrophages cell lines from both normal mice (Lps n ) and mice genetically unresponsive to LPS (Lps d ), whereas only Lps n macrophages made these responses to LPS. Surprisingly, LPS treatment of Lps d macrophages induced a rise in ceramide similar to that observed in LPS-responsive cells. These results indicate that the wild type Lps allele is not required for LPSinduced ceramide generation and suggest that ceramide elevation alone is insufficent stimulus for most responses to LPS.

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Mouse macrophage clones immortalized by retroviruses are functionally heterogeneous.

Abstract: Murine macrophage clones were generated from thymus, spleen, brain, and bone marrow by in vitro immortalization with recombinant retroviruses carrying an avian v-myc oncogene. The cloned cell lines express F4/80 molecules, exert phagocytosis, have nonspecific esterase activ-

Cited by 34 publications

References 28 publications

C/EBPβGene Inactivation Causes Both Impaired and Enhanced Gene Expression and Inverse Regulation of IL-12 p40 and p35 mRNAs in Macrophages

C/EBPβGene Inactivation Causes Both Impaired and Enhanced Gene Expression and Inverse Regulation of IL-12 p40 and p35 mRNAs in Macrophages

The v-myc oncogene

Role of Ceramide in Lipopolysaccharide (LPS)-induced Signaling

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