* Department of Immunology, Lerner Research Institute, and
The Cole Eye Institute, The Cleveland Clinic Foundation, Ohio;
Division of Biology, University of California, San Diego; and
Division of Monoclonal Antibodies, Center for Biologics Evaluation and Research, Bethesda, Maryland
Correspondence: Andrew C. Larner, The Cleveland Clinic Foundation, Department of Immunology, NB3-30, 9500 Euclid Avenue, Cleveland, OH 44195. E-mail: larnera{at}ccf.org
Type I interferon (IFN)-
/ß and type II IFN-
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-ß or IFN- 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--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- signaling.
Key Words: Jak • Akt • cytokine • MAPK • ERK
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