title: The nuclear factor-kappaB-interleukin-6 signalling pathway mediating vascular inflammation.
abstract: Vascular inflammation is a common pathophysiological response to diverse cardiovascular disease processes, including atherosclerosis, myocardial infarction, congestive heart failure, and aortic aneurysms/dissection. Inflammation is an ordered process initiated by vascular injury that produces enhanced leucocyte adherence, chemotaxis, and finally activation in situ. This process is coordinated by local secretion of adhesion molecules, chemotactic factors, and cytokines whose expression is the result of vascular injury-induced signal transduction networks. A wide variety of mediators of the vascular injury response have been identified; these factors include vasoactive peptides (angiotensin II, Ang II), CD40 ligands, oxidized cholesterol, and advanced glycation end-products. Downstream, the nuclear factor-kappaB (NF-kappaB) transcription factor performs an important signal integration step, responding to mediators of vascular injury in a stimulus-dependent and cell type-specific manner. The ultimate consequence of NF-kappaB signalling is the activation of inflammatory genes including adhesion molecules and chemotaxins. However, clinically, the hallmark of vascular NF-kappaB activation is the production of interleukin-6 (IL-6), whose local role in vascular inflammation is relatively unknown. The recent elucidation for the role of the IL-6 signalling pathway in Ang II-induced vascular inflammation as one that controls monocyte activation as well as its diverse signalling mechanism will be reviewed. These new discoveries further our understanding for the important role of the NF-kappaB-IL-6 signalling pathway in the process of vascular inflammation.
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Sealy Center for Molecular Medicine and Institute for Translational Sciences, University of Texas Medical Branch, MRB 8.122, 301 University Blvd, Galveston, TX 77555-1060, USA. arbrasie@utmb.edu
authors.forename: Allan R
authors.initials: AR
authors.lastname: Brasier
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D018836:Inflammation Mediators / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology*; D015398:Signal Transduction
chemical_list: D018836:Inflammation Mediators; D015850:Interleukin-6; D016328:NF-kappa B