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Cell type specific expression and regulation of murine interferon alpha and beta genes
A Hoss-Homfeld1, E C Zwarthoff, R Zawatzky
1Institute of Virus Research, German Cancer Research Center, Heidelberg, Federal Republic of Germany.
Abstract:
The differential and cell type specific expression of various murine IFN alpha genes and IFN beta was examined by S1 nuclease protection assays in M-CSF cultured C57BL/6 mouse bone marrow macrophages and L929 fibroblasts. In Newcastle disease virus (NDV) induced macrophages, IFN beta, alpha 2, alpha 4, and alpha 1 mRNAs were the predominant species, whereas IFN alpha 6 and alpha 9 transcripts accounted for only 5% of total IFN alpha mRNAs. In L929 cells, only IFN beta, alpha 2, and alpha 4 genes were expressed efficiently following NDV induction and IFN alpha 9 mRNA was always below detectable level. Induction of macrophages with the synthetic inducer 10-carboxymethyl-9-acridanone resulted in small amounts of IFN alpha 2, alpha 4, and alpha 6 mRNAs and the IFN beta mRNA level was about 100-fold higher. Macrophages and L929 cells especially differed in the kinetics of IFN gene induction in that macrophages showed a much earlier transient expression of all IFN mRNA species. Additionally, IFN transcripts were degraded much faster in macrophage cultures than in L929cells. The IFN response of macrophages is thus characterized by a highly efficient control, providing a rapid onset and a rapid decline of IFN production, which limits release of IFN to a short time interval.
Insights
Mouse macrophages and L929 fibroblasts show distinct interferon (IFN) gene expression patterns. Macrophages exhibit rapid, transient IFN production, unlike fibroblasts, highlighting efficient immune response control.
Area of Science:
- Immunology
- Molecular Biology
- Virology
Background:
- Interferons (IFNs) are crucial cytokines in antiviral immunity.
- Cell type-specific differences in IFN gene expression are not fully understood.
Purpose of the Study:
- To investigate the differential and cell type-specific expression of murine interferon alpha (IFN-α) and interferon beta (IFN-β) genes.
- To compare the kinetics and regulation of IFN gene induction between macrophages and fibroblasts.
Main Methods:
- S1 nuclease protection assays were used to quantify mRNA levels.
- Murine bone marrow-derived macrophages and L929 fibroblasts were cultured and induced with Newcastle disease virus (NDV) or a synthetic inducer (10-carboxymethyl-9-acridanone).
Main Results:
- Macrophages predominantly expressed IFN-β, IFN-α2, IFN-α4, and IFN-α1 upon NDV induction, with IFN-α6 and IFN-α9 being minor species.
- L929 cells efficiently expressed IFN-β, IFN-α2, and IFN-α4, with undetectable IFN-α9.
- Synthetic inducer treatment of macrophages resulted in low levels of IFN-α2, IFN-α4, IFN-α6, and a 100-fold higher IFN-β level.
- Macrophages displayed earlier, transient IFN mRNA expression and faster transcript degradation compared to L929 cells.
Conclusions:
- Macrophages exhibit a tightly regulated IFN response characterized by rapid onset and decline.
- This rapid IFN production limits the release interval, suggesting a controlled immune signaling mechanism.
- Cell type-specific differences in IFN gene expression and kinetics are significant for immune response modulation.