Induction of Endothelial-Leukocyte Interaction by Interferon-g Requires Coactivation of Nuclear Factor-kB

To determine whether nuclear factor (NF)-kB is necessary to confer endothelial cell responsiveness to interferon (INF)-g in terms of vascular cell adhesion molecule (VCAM)-1 expression and leukocyte adhesion, human endothelial cells were treated with IFN-g in the presence of low concentrations (LCs) of interleukin (IL)-1a (#100 pg/mL), which activates NF-kB but does not induce VCAM-1 expression. Although IFN-g induced major histocompatibility complex class II antigen expression and although a high concentration of IL-1a (10 ng/mL) induced leukocyte adhesion and VCAM-1 expression, neither IFN-g nor LC IL-1a was able to induce VCAM-1 expression or leukocyte adhesion. However, the combination of IFN-g and LC IL-1a induced VCAM-1 expression and increased leukocyte adhesion (67% and 49% of high-concentration IL-1a, respectively). Electrophoretic mobility shift assays and immunoblotting of nuclear extracts showed that IFN-g activated signal transducers and activators of transcription (STAT)-1a and interferon regulatory factor (IRF)-1 but not NF-kB, whereas LC IL-1a activated NF-kB but not STAT-1a or IRF-1. Nuclear run-on studies showed that LC IL-1a is necessary but not sufficient for inducing VCAM-1 gene transcription and that the combination of IFN-g and LC IL-1a is required for full VCAM-1 gene transcription. These findings suggest that factors that activate NF-kB can synergize with IFN-g in promoting endothelial-leukocyte interaction. (Arterioscler Thromb Vasc Biol. 2001;21:227-232.)