Interferon-gamma transcriptionally modulates the expression of the genes for the high affinity IgG-Fc receptor and the 47-kDa cytosolic component of NADPH oxidase in human polymorphonuclear leukocytes.
We examined the mechanisms responsible for the regulation by interferon-gamma (IFN-gamma) of the expression of the genes encoding the high affinity IgG-Fc receptor (Fc gamma R-I, CD64) and the NADPH oxidase 47-kDa cytosolic factor (p47-phox) in human polymorphonuclear leukocytes (PMN). Nuclear run-on transcriptional assays demonstrated that the Fc gamma R-I gene transcription is undetectable in untreated PMN but is significantly induced by IFN-gamma. Unlike Fc gamma R-I, p47-phox gene transcription is constitutively active in resting PMN and is down-regulated by a 2-h treatment of these cells with IFN-gamma. The transcriptional modulation by IFN-gamma of Fc gamma R-I and p47-phox genes is not influenced by the protein synthesis inhibitor cycloheximide. Moreover, Northern blot analysis revealed that cycloheximide superinduces p47-phox mRNA expression by increasing its half-life and without affecting p47-phox gene transcription. These findings indicate that human PMN can regulate gene expression by transcriptional and posttranscriptional events.
Cassatella
M A
MA
Institute of General Pathology, Università di Verona, Italy.
Bazzoni
F
F
Calzetti
F
F
Guasparri
I
I
Rossi
F
F
Trinchieri
G
G
D000943:Antigens, Differentiation / Q000235:genetics*; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003600:Cytosol / Q000201:enzymology; D003609:Dactinomycin / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D009247:NADH, NADPH Oxidoreductases / Q000097:blood / Q000235:genetics*; D019255:NADPH Oxidases; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D012333:RNA, Messenger / Q000097:blood / Q000187:drug effects / Q000235:genetics; D011961:Receptors, Fc / Q000235:genetics*; D017452:Receptors, IgG; D011994:Recombinant Proteins; D014158:Transcription, Genetic / Q000187:drug effects*
D000943:Antigens, Differentiation; D007074:Immunoglobulin G; D012333:RNA, Messenger; D011961:Receptors, Fc; D017452:Receptors, IgG; D011994:Recombinant Proteins; D003609:Dactinomycin; D007371:Interferon-gamma; D003513:Cycloheximide; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases