Tissue-specific and inducer-specific differential induction of ISG56 and ISG54 in mice.
The interferon-stimulated genes (ISGs) ISG56 and ISG54 are strongly induced in cultured cells by type I interferons (IFNs), viruses, and double-stranded RNA (dsRNA), which activate their transcription by various signaling pathways. Here we studied the stimulus-dependent induction of both genes in vivo. dsRNA, which is generated during virus infection, induced the expression of both genes in all organs examined. Induction was not seen in STAT1-deficient mice, indicating that dsRNA-induced gene expression requires endogenous IFN. We further examined the regulation of these ISGs in several organs from mice injected with dsRNA or IFN-beta. Both ISG56 and ISG54 were widely expressed and at comparable levels. However, in organs isolated from mice injected with IFN-alpha the expression of ISG54 was reduced and more restricted in distribution compared with the expression level and distribution of ISG56. When we began to study specific cell types, splenic B cells showed ISG54 but not ISG56 expression in response to all agonists. Finally, in livers isolated from mice infected with vesicular stomatitis virus, the expression of ISG56, but not ISG54, was induced; this difference was observed at both protein and mRNA levels. These studies have revealed unexpected complexity in IFN-stimulated gene induction in vivo. For the first time we showed that the two closely related genes are expressed in a tissue-specific and inducer-specific manner. Furthermore, our findings provide the first evidence of a differential pattern of expression of ISG54 and ISG56 genes by IFN-alpha and IFN-beta.
Terenzi
Fulvia
F
Department of Molecular Genetics/NE20, The Lewrnert research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
White
Christine
C
Pal
Srabani
S
Williams
Bryan R G
BR
Sen
Ganes C
GC
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation; D016898:Interferon-alpha / Q000494:pharmacology / Q000502:physiology*; D016899:Interferon-beta / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012330:RNA, Double-Stranded / Q000494:pharmacology; D050794:STAT1 Transcription Factor / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology; D014018:Tissue Distribution; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D015854:Up-Regulation; D014721:Vesicular stomatitis Indiana virus
D000906:Antibodies; C522692:ISG54 protein, mouse; C522693:ISG56 protein, mouse; D016898:Interferon-alpha; D012330:RNA, Double-Stranded; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D014157:Transcription Factors; D016899:Interferon-beta