Interleukin-4 prevents the induction of G-CSF mRNA in human adherent monocytes in response to endotoxin and IL-1 stimulation.
Human recombinant interleukin-4 (IL-4) was studied for its effects on the expression of granulocyte-colony stimulating factor (G-CSF) mRNA in human adherent monocytes in the absence and presence of endotoxin and interleukin 1 (IL-1). IL-4 (15 ng/ml) did not induce G-CSF transcripts in monocytes but suppressed the endotoxin-induced G-CSF expression when added simultaneously. Sequential treatment of monocytes with IL-4 followed by endotoxin suppressed G-CSF mRNA induction totally. This effect was independent of the presence of fetal bovine serum but dependent of the IL-4 dose. Comparable results were obtained with IL-1. IL-1 (50 U/ml) induced G-CSF expression in human adherent monocytes which could be counteracted by IL-4 pretreatment. In addition, it was shown that the induction of G-CSF mRNA by the calcium-ionophore A23187 or by c-AMP elevating agents could be blocked by IL-4. These suppressive effects of IL-4 were not related to changes in the half-life of G-CSF mRNA and were independent of protein synthesis. Finally it was demonstrated that IL-4 had comparable effects on the G-CSF secretion of endotoxin and IL-1 stimulated human monocytes by using a murine bone marrow assay. These results indicate that IL-4 down-regulates the expression of G-CSF gene and secretion of proteins in human activated monocytes.
Vellenga
E
E
Department of Medicine, University of Groningen, The Netherlands.
Dokter
W
W
de Wolf
J T
JT
van de Vinne
B
B
Esselink
M T
MT
Halie
M R
MR
D015152:Blotting, Northern; D002448:Cell Adhesion; D002478:Cells, Cultured; D004731:Endotoxins / Q000276:immunology; D005786:Gene Expression Regulation / Q000502:physiology; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics*; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics*; D009000:Monocytes / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis*; D011994:Recombinant Proteins / Q000235:genetics
D004731:Endotoxins; D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D015847:Interleukin-4