Granulocyte-colony stimulating factor inhibits TNFalpha production in a human hepatoma cell line.
The syndrome of cachexia associated with malignant diseases can be in part attributed to the effects of tumour necrosis factor alpha (TNFalpha) which itself is produced by a variety of tumour cells. We have recently reported that the human hepatoma cell line HepG2 expresses the TNFalpha gene and releases biologically active TNFalpha protein after stimulation with interleukin-1beta (IL-1beta). Granulocyte-colony stimulating factor (G-CSF) is a glycoprotein necessary for the proliferation and differentiation of neutrophil progenitor cells in the bone marrow. In addition G-CSF has been reported to exert anti-inflammatory effects. In our study we tested the effect of recombinant human G-CSF (rhG-CSF) on TNFalpha production in HepG2 cells. It could be shown that rhG-CSF (250 U/ml) significantly reduced IL-1beta-induced (300 pg/ml) TNFalpha gene expression after 1-h and 3-h incubation periods (TNFalpha mRNA concentrations were: 8.8+/-2.1 amol/ microg total RNA after a 1-h incubation with IL-1beta versus 3.8+/-1.3 amol/ microg total RNA after a 1-h incubation with IL-1beta + rhG-CSF and 13.8+/-2.2 amol/ microg total RNA after a 3-h incubation with IL-1beta versus 8.8+/-2. 1 amol/ microg total RNA after a 3-h incubation with IL-1beta + rhG-CSF). From these data we conclude that rhG-CSF is a potent inhibitor of cytokine-induced TNFalpha production by tumour cells. Therefore, treatment of patients with malignant diseases with rhG-CSF might represent a useful tool to improve the tumour-associated cachexia.
Frede
S
S
Department of Physiology I, University of Bonn, Nussallee 11, D-53115 Bonn, Germany.
Deetjen
C
C
Schobersberger
W
W
Hoffmann
G
G
D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D015870:Gene Expression; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007700:Kinetics; D008113:Liver Neoplasms / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D007375:Interleukin-1; D016328:NF-kappa B; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor