IL-10-induced factors belonging to the p91 family of proteins bind to IFN-gamma-responsive promoter elements.
Expression of the gene encoding the high affinity IgG receptor (Fc gamma RI) is stimulated by IFN-gamma through a promoter element designated gamma-IFN activation site (GAS). This sequence binds a transcription factor designated gamma-IFN activation factor (GAF). GAF-GAS complexes contain an IFN-regulated 91-kDa protein (p91). In mouse peritoneal macrophages, IL-4 and IL-10 influenced both basal and IFN-gamma-induced expression of Fc gamma RI in opposite ways: IL-10 was stimulatory and IL-4 repressed Fc gamma RI expression. IL-4 or IL-10 did not affect the activation of GAF by IFN-gamma, but both activated the binding of latent, receptor-activated factors (RAFTs) to the Fc gamma RI GAS. RAFTs-IL-4 and -IL-10 migrated similarly in electrophoretic mobility shift assays but could be distinguished through their specificities for different GAS sequences and their reactivity with anti-p91 antisera. These experiments also revealed two distinct RAFTs-IL-10 to be members of the p91 family of proteins. The data suggest GAS-related elements to integrate signals from IFN-gamma-, IL-4- and IL-10-activated signaling paths.
Lehmann
J
J
Fraunhofer-Institute of Toxicology and Molecular Biology, Hannover, Germany.
Seegert
D
D
Strehlow
I
I
Schindler
C
C
Lohmann-Matthes
M L
ML
Decker
T
T
D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000502:physiology*; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D017452:Receptors, IgG / Q000235:genetics*; D050794:STAT1 Transcription Factor; D015534:Trans-Activators
D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D017452:Receptors, IgG; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma