Mouse genotype affects inducible expression of cytokine genes.
The levels of circulating IFN in mice infected with Newcastle disease virus (NDV) are regulated by the If-1 locus. In this study we show that in NDV-infected C57BL/6 mice, which carry the If-1h allele and produce high levels of IFN, high levels of both IFN-alpha and -beta mRNA can be detected in the spleen. In contrast, only very low levels of IFN mRNA could be detected in spleens of infected BALB/c mice containing the If-1l allele and producing low levels of IFN or in B6.C-H28c mice that are congenic for the If-1l allele. The relative levels of all individual IFN-alpha 1, alpha 4, and alpha 6 mRNA in spleens of infected BALB/c were lower than in spleens of infected C57BL/6 mice, indicating that the If-1 locus affects the expression of all IFN-alpha subtypes and is not associated with the deletion or inactivation of a specific IFN gene. The relative levels of IFN regulatory factor-1 mRNA in infected mice carrying the If-1l and If-1h loci were comparable, suggesting that the If-1 regulation is not associated with the altered expression of the IFN regulatory factor-1 gene. Quantitative difference in the expression of IFN-alpha and -beta genes was also observed in in vitro-infected peritoneal macrophages isolated from either C57BL/6 or BALB/c mice. A surprise finding was that the If-1 locus also affected the NDV-induced expression of two other cytokine genes, TNF-alpha and IL-6. Priming of the macrophage cultures with murine IFN enhanced the expression of all cytokine genes, and the relative levels of IFN, TNF-alpha, and IL-6 mRNA induced by NDV in macrophages derived from C57BL/6 and BALB/c mice were comparable. We propose that the If-1 locus affects the early stages of a signal transduction pathway which are common to the virus-mediated induction of IFN, TNF-alpha, and IL-6 genes.
Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
N B
NB
Raj
S C
SC
Cheung
I
I
Rosztoczy
P M
PM
Pitha
D000818:Animals; D016207:Cytokines / Q000235:genetics*; D015870:Gene Expression; D005809:Genes, Regulator; D005838:Genotype; D007372:Interferons / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D009521:Newcastle Disease / Q000503:physiopathology*; D009522:Newcastle disease virus / Q000276:immunology; D010529:Peritoneal Cavity / Q000166:cytology; D012333:RNA, Messenger / Q000235:genetics; D013154:Spleen / Q000503:physiopathology
D016207:Cytokines; D012333:RNA, Messenger; D007372:Interferons