Modulation by interferon-gamma of the production and gene expression of IL-1 receptor antagonist in human neutrophils.
In this report, we show that interferon-gamma (IFN-gamma) modulates the production of IL-1ra in activated human neutrophils. In lipopolysaccharide-stimulated cells, IFN-gamma increased the release of IL-1ra without modulating IL-1ra mRNA accumulation; under these conditions, IFN-gamma only marginally enhanced IL-1ra de novo synthesis, while IL-1ra was more efficiently secreted. In response to the formylated peptide, fMLP, neutrophils released small but significant amounts of IL-1ra, yet without an increase in IL-1ra mRNA over constitutive levels. Following IFN-gamma treatment, however, the fMLP-elicited IL-1ra production was greatly potentiated, and this was accompanied by a transient increased accumulation of IL-1ra mRNA. Finally, opsonized yeast particles were found to induce IL-1ra formation at late incubation times, and prior treatment of neutrophils with IFN-gamma moderately enhanced this response. Collectively, our results demonstrate that in neutrophils activated by different classes of agonists, IFN-gamma modulates the release of IL-1ra by acting through distinct mechanisms.
McDonald
P P
PP
Institute of General Pathology, Verona, Italy.
Gasperini
S
S
Calzetti
F
F
Cassatella
M A
MA
D002478:Cells, Cultured; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D053590:Interleukin 1 Receptor Antagonist Protein; D008070:Lipopolysaccharides / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D012795:Sialoglycoproteins / Q000096:biosynthesis* / Q000235:genetics
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D009240:N-Formylmethionine Leucyl-Phenylalanine; D007371:Interferon-gamma