This Article Full Text Full Text (PDF) Data Supplement Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by De Caterina, R. Articles by Liao, J. K. Search for Related Content PubMed PubMed Citation Articles by De Caterina, R. Articles by Liao, J. K. Related Collections Endothelium/vascular type/nitric oxide Gene expression Gene regulation Growth factors/cytokines

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:227.)
© 2001 American Heart Association, Inc.

Vascular Biology

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

Raffaele De Caterina; Todd Bourcier; Ulrich Laufs; Vito La Fata; Guido Lazzerini; Andrew S. Neish; Peter Libby; James K. Liao

From the Vascular Medicine Unit (T.B., U.L., V.L.F., P.L., J.K.L.), Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass; the CNR Institute of Clinical Physiology (R.D.C., G.L.), Pisa, and the Cardiovascular Division (R.D.C., G.L.), "G. D’Annunzio" University, Chieti, Italy; and the Department of Pathology (A.S.N.), Emory University Hospital, Atlanta, Ga.

Correspondence to James K. Liao, MD, Vascular Medicine and Atherosclerosis Unit, Brigham and Women’s Hospital, 221 Longwood Ave, LMRC-322, Boston, MA 02115. E-mail jliao{at}rics.bwh.harvard.edu

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

Key Words: endothelium • adhesion molecules • cytokines • inflammation

This article has been cited by other articles:

				V. Fuster, P. R. Moreno, Z. A. Fayad, R. Corti, and J. J. Badimon Atherothrombosis and High-Risk Plaque: Part I: Evolving Concepts J. Am. Coll. Cardiol., September 20, 2005; 46(6): 937 - 954. [Abstract] [Full Text] [PDF]

				J. H. Von der Thusen, J. Kuiper, T. J. C. Van Berkel, and E. A. L. Biessen Interleukins in Atherosclerosis: Molecular Pathways and Therapeutic Potential Pharmacol. Rev., March 1, 2003; 55(1): 133 - 166. [Abstract] [Full Text] [PDF]

				H. M. Dansky, P. Shu, M. Donavan, J. Montagno, D. L. Nagle, J. S. Smutko, N. Roy, S. Whiteing, J. Barrios, T. J. McBride, et al. A Phenotype-Sensitizing Apoe-Deficient Genetic Background Reveals Novel Atherosclerosis Predisposition Loci in the Mouse Genetics, April 1, 2002; 160(4): 1599 - 1608. [Abstract] [Full Text] [PDF]