Induction of Endothelial-Leukocyte Interaction by Interferon-\(\gamma\) Requires Coactivation of Nuclear Factor-\(\kappa\)B
De Caterina_InductionOfAndothelial-LeukocyteInteraction_ATVB_2001.pdf (1.650Mb)
Access StatusFull text of the requested work is not available in DASH at this time ("dark deposit"). For more information on dark deposits, see our FAQ.
De Caterina, Raffaele
La Fata, Vito
Neish, Andrew S.
Liao, James K.
MetadataShow full item record
CitationDe 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.
AbstractTo 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.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:12763593
- HMS Scholarly Articles