Identification and characterization of a novel monocyte/macrophage differentiation-dependent gene that is responsive to lipopolysaccharide, ceramide, and lysophosphatidylcholine.
A novel differentiation-dependent cDNA (DIF-2) has been isolated from human mononuclear phagocytes by differential display. The full-length cDNA was cloned and sequenced. DIF-2 consists of 156 amino acids and has a predicted isoelectric point of 8.84. The mRNA is expressed in freshly isolated monocytes and is downregulated significantly when monocytes are subjected to differentiation. A similar differentiation-dependent downregulation is observed in normal hepatocytes compared to undifferentiated HepG2 cells. The mRNA expression in monocytes is sensitive to lipopolysaccharide and ceramide which both strongly increase DIF-2 transcription, while lysophosphatidylcholine results in a weaker upregulation of DIF-2 expression. A DIF-2 homologous gene has been previously isolated from mouse fibroblasts and was shown to be a serum growth factor-inducible immediate early gene. Our results indicate that DIF-2 represents a gene which is regulated in differentiation processes and strongly responsive to lipopolysaccharide, ceramide and lysophosphatidylcholine.
Pietzsch
A
A
Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Germany.
Büchler
C
C
Aslanidis
C
C
Schmitz
G
G
D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D002454:Cell Differentiation; D002478:Cells, Cultured; D002518:Ceramides / Q000494:pharmacology*; D003001:Cloning, Molecular; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects*; D006023:Glycoproteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D017874:Immediate-Early Proteins; D007526:Isoelectric Point; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009363:Neoplasm Proteins; D010750:Phosphoproteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D051017:Apoptosis Regulatory Proteins; D002518:Ceramides; D006023:Glycoproteins; C099815:IER3 protein, human; D017874:Immediate-Early Proteins; D008070:Lipopolysaccharides; D008244:Lysophosphatidylcholines; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D013755:Tetradecanoylphorbol Acetate