Abstract
Interleukin-1 (IL-1) is a proinflammatory cytokine that participates in the activation of the acute-phase plasma protein genes in hepatic cells during infection and injury. In human hepatoma HepG2 and Hep3B cells, IL-1 beta induced production of the granulocyte colony-stimulating factor (G-CSF) in a dose-dependent manner. Activation of G-CSF gene expression was an early and transient response. In HepG2 cells, G-CSF mRNA was strongly upregulated 2 hours after IL-1 beta treatment and returned to the pretreatment level by 6 hours. The secreted G-CSF was biologically active, as shown by the induction of gene transcription through the G-CSF receptor. Maximal G-CSF activity released to culture medium occurred after 8 hours. Previous studies have shown that liver expression of G-CSF was augmented in mice challenged by inflammatory stimuli. Our data suggest that IL-1 beta mediates, at least in part, this cytokine activation program in parenchymal cells and that liver-derived G-CSF may contribute to the regulation of hematopoiesis during the acute-phase response.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acute-Phase Reaction / chemically induced*
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Culture Media, Conditioned / chemistry
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Dose-Response Relationship, Drug
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Gene Expression Regulation, Neoplastic / drug effects*
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Genetic Vectors
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Granulocyte Colony-Stimulating Factor / biosynthesis*
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Hematoma / metabolism*
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Hematoma / pathology
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Humans
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Interleukin-1 / pharmacology*
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Interleukin-6 / pharmacology
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Liver Neoplasms / metabolism*
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Liver Neoplasms / pathology
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Neoplasm Proteins / biosynthesis*
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RNA, Messenger / biosynthesis
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RNA, Neoplasm / biosynthesis
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Receptors, Granulocyte Colony-Stimulating Factor / genetics
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Receptors, Granulocyte Colony-Stimulating Factor / metabolism
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Recombinant Fusion Proteins / metabolism
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Recombinant Fusion Proteins / pharmacology
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Transcription, Genetic
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Transfection
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Tumor Cells, Cultured / drug effects
Substances
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Culture Media, Conditioned
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Interleukin-1
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Interleukin-6
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Neoplasm Proteins
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RNA, Messenger
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RNA, Neoplasm
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Receptors, Granulocyte Colony-Stimulating Factor
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Recombinant Fusion Proteins
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Granulocyte Colony-Stimulating Factor