Interleukin-1 beta induces production of granulocyte colony-stimulating factor in human hepatoma cells.
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.
Lai
C F
CF
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Baumann
H
H
D000210:Acute-Phase Reaction / Q000139:chemically induced*; D017077:Culture Media, Conditioned / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005822:Genetic Vectors; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis*; D006406:Hematoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects
D017077:Culture Media, Conditioned; D007375:Interleukin-1; D015850:Interleukin-6; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011993:Recombinant Fusion Proteins; D016179:Granulocyte Colony-Stimulating Factor