Role of interferon regulatory factor 1 in monocyte/macrophage differentiation.
Interferon regulatory factor-1 (IRF-1) has been recognized as an important tumor suppressor and growth regulatory transcription factor, which is also involved in cell differentiation. In this study we investigated the role of IRF-1 in phorbol 12-myristate 13-acetate (PMA)-induced monocyte/macrophage differentiation of human monoblastic U937 cells. For this purpose U937 cells were stably transfected with a vector overexpressing IRF-1 antisense mRNA (U937 IRF-1A cells) and with the SV-40 empty vector (U937-SV40 e.v. cells). We report here that U937 and U937-SV40 e.v. cells differentiated into macrophage-like cells upon PMA stimulation and showed IRF-1 up-regulation. On the contrary, U937 IRF-1A cells stimulated with PMA kept an undifferentiated phenotype and proliferated actively. A direct correlation between induction of IRF-1 and up-regulation of IRF-1 gene targets such as ornithine decarboxylase (ODC) and WAF-1/CIP-1 was also observed in U937 cells. On the other hand U937 IRF-1A cells down-regulated ODC and did not express WAF-1. Results show that IRF-1 plays a pivotal role in PMA-induced monocyte/macrophage differentiation.
Manzella
L
L
Istituto di Patologia Generale Università di Catania, Catania, Italy.
Conte
E
E
Cocchiaro
G
G
Guarniera
E
E
Sciacca
B
B
Bonaiuto
C
C
Stagno
F
F
Messina
A
A
D002454:Cell Differentiation / Q000276:immunology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000378:metabolism / Q000502:physiology; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D009955:Ornithine Decarboxylase / Q000378:metabolism / Q000502:physiology; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology; D014407:Tumor Cells, Cultured; D020298:U937 Cells / Q000201:enzymology / Q000378:metabolism
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D010750:Phosphoproteins; D014157:Transcription Factors; C016658:phorbolol myristate acetate; D007371:Interferon-gamma; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate