Tumor Necrosis Factor Receptor and Ligand Superfamily Family Members TNFRSF14 and LIGHT

Abstract

Increasing evidence indicates that atherosclerosis is the consequence of complex, multifactorial processes involving the abnormal interplay between local mechanisms involved in lipoprotein metabolism, the extracellular matrix and coagulation proteins, endothelial and smooth muscle cells, mononuclear leukocytes, and growth factors/cytokines.1,2 A number of cytokines including those activating several members of the tumor necrosis factor (TNF) receptor superfamily have been consistently identified in atherosclerotic lesions and implicated in the pathogenesis of atherosclerosis. One of the earliest responses to hypercholesterolemia is an increase in the adherence of monocytes to arterial endothelium and then penetration into the intima. TNF-α together with interleukin (IL)-1β increases the adherence of leukocytes to endothelial cells,3 and in young ApoE-deficient mice, they promote monocyte accumulation within developing atherosclerotic lesions.4 See page 2004 In established lesions, the actions and patterns of expression of TNF receptor superfamily (TNFRSF) members and their activating ligands is complex and, in most cases, seems to lead to the development of complex atherosclerotic lesions that are susceptible to rupture. TNFRSF members are defined as those structurally related to the first family members TNFR1 and TNFR2, (now TNFRSF1A and TNFRSF1B, respectively).5 Each member contains multiple copies of a cysteine-rich motif of approximately 40 amino acids that is known to provide the ligand recognition motif; their cytoplasmic regions are frequently capable of stimulating the transcription factors activator protein-1 and nuclear factor-κB. The latter factor is involved in regulating numerous genes critical for inflammatory responses, including IL-6, IL-8, vascular cell adhesion molecule-1, and E-selectin.6 A number of receptors also contain …