A PI-3 kinase-dependent, Stat1-independent signaling pathway regulates interferon-stimulated monocyte adhesion.
Type I interferon (IFN)-alpha/beta and type II IFN-gamma induce the expression of early response genes through activation of the Janus tyrosine kinase/signal transducer and activator of transcription ( Stat) pathway. Although IFNs regulate a variety of other signaling cascades, little is known about how they contribute to the biological activities of these cytokines. In this study, we demonstrate that IFN-beta or IFN-gamma induces the phosphorylation of the serine/threonine kinase Akt in primary human peripheral blood monocytes. Abrogation of the IFN- stimulated Akt activation by phosphatidylinositol-3 kinase ( PI-3K) inhibitors prevents IFN-induced adhesion in these cells, and IFN activation of the Stat1-dependent guanylate- binding protein ( GBP) gene is not affected. Importantly, Stat1-deficient bone marrow macrophages displayed a similar level of IFN-gamma-stimulated adhesion compared with macrophages derived from wild-type littermates. These findings demonstrate for the first time that IFN stimulation of a PI-3K signaling cascade modulates the ability of these cytokines to regulate monocyte adhesion, and this process does not require the expression of Stat1, a primary mediator of IFN-gamma signaling.[1]References
- A PI-3 kinase-dependent, Stat1-independent signaling pathway regulates interferon-stimulated monocyte adhesion. Navarro, A., Anand-Apte, B., Tanabe, Y., Feldman, G., Larner, A.C. J. Leukoc. Biol. (2003) [Pubmed]
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