IFN-gamma-induced upregulation of Fcgamma-receptor-I during activation of monocytic cells requires the PKR and NFkappaB pathways
Abstract
Interferon (IFN)-gamma is a potent activator of macrophages, increasing the cells capacity to perform specific functions during inflammation and immune response. In this report we use IFN-gamma-induced upregulation of the high affinity receptor for IgG (FcgammaRI/CD64) in the human monocytic cell line U-937 as a model for monocytic activation. We show that upregulation of FcgammaRI is dependent on signals mediated by the dsRNA-dependent kinase PKR, and the transcription factor NFkappaB. Silencing of PKR expression by siRNA or inhibition of PKR by 2-aminopurine (2-AP) potently blocks the IFN-gamma-induced transcriptional activation of the FcgammaRI promoter. We find that the serine 727 phosphorylation of Stat1, required for full IFN-gamma-induced FcgammaRI promoter activity, is dependent on PKR. We further show that IFN-gamma induction of FcgammaRI upregulation is dependent on the NFkappaB pathway, as evidenced by inhibition of NFkappaB using a phosphorylation defective IkappaBalpha (S32A/S36A) mutant, or inhibiting the IkappaB-kinase (IKK) by treatment with BMS345541. Our results suggest that IFN-gamma-induced increase of FcgammaRI expression requires the integration of two signalling events: PKR-dependent Stat1 serine 727 phos...Continue Reading
References
Citations
Related Concepts
Related Feeds
Bioinformatics in Biomedicine
Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.
Antibody-Dependent Cell Cytotoxicity
Antibody-dependent cellular toxicity refers to the lysis of a target cell by a non-sensitized effector cell of the immune system as a result of antibodies binding to the target cell membrane and engaging the Fc receptors on the immune effector cells. Find the latest research on antibody-dependent cellular toxicity here.