De Caterina, RaffaeleBourcier, ToddLaufs, UlrichLa Fata, VitoLazzerini, GuidoNeish, Andrew S.Libby, PeterLiao, James K.2014-09-022001De Caterina, Raffaele, Todd Bourcier, Ulrich Laufs, Vito La Fata, Guido Lazzerini, Andrew S. Neish, Peter Libby, and James K. Liao. 2001. “Induction of Endothelial-Leukocyte Interaction by Interferon-\(\gamma\) Requires Coactivation of Nuclear Factor-\(\kappa\)B.” Arteriosclerosis, Thrombosis, and Vascular Biology 21 (2) (February 1): 227–232. doi:10.1161/01.atv.21.2.227. http://dx.doi.org/10.1161/01.ATV.21.2.227.1079-56421524-4636http://nrs.harvard.edu/urn-3:HUL.InstRepos:12763593To determine whether nuclear factor (NF)-\(\kappa\) B is necessary to confer endothelial cell responsiveness to interferon (INF)-\(\gamma\) in terms of vascular cell adhesion molecule (VCAM)-1 expression and leukocyte adhesion, human endothelial cells were treated with IFN-\(\gamma\) in the presence of low concentrations (LCs) of interleukin (IL)-1\(\alpha\) (≤100 pg/mL), which activates \(NF-\kappa B\) but does not induce VCAM-1 expression. Although IFN-\(\gamma\) induced major histocompatibility complex class II antigen expression and although a high concentration of IL-1\(\alpha\) (10 ng/mL) induced leukocyte adhesion and VCAM-1 expression, neither IFN-\(\gamma\) nor LC IL-1\(\alpha\) was able to induce VCAM-1 expression or leukocyte adhesion. However, the combination of IFN-\(\gamma\) and LC IL-1\(\alpha\) induced VCAM-1 expression and increased leukocyte adhesion (67% and 49% of high-concentration IL-1\(\alpha\), respectively). Electrophoretic mobility shift assays and immunoblotting of nuclear extracts showed that IFN-\(\gamma\) activated signal transducers and activators of transcription (STAT)-1\(\alpha\) and interferon regulatory factor (IRF)-1 but not \(NF-\kappa B\), whereas LC IL-1\(\alpha\) activated \(NF-\kappa B\) but not STAT-1\(\alpha\) or IRF-1. Nuclear run-on studies showed that LC IL-1\(\alpha\) is necessary but not sufficient for inducing VCAM-1 gene transcription and that the combination of IFN-\(\gamma\) and LC IL-1\(\alpha\) is required for full VCAM-1 gene transcription. These findings suggest that factors that activate \(NF-\kappa B\) can synergize with IFN-\(\gamma\) in promoting endothelial-leukocyte interaction.en-USendotheliumadhesion moleculescytokinesinflammationJournal Article2014-09-0210.1161/01.ATV.21.2.227