Description: TWEAK, TNF-like weak inducer of apoptosis, is a member of the TNF family of proteins. TWEAK has the same sequence as APO-3 ligand. Based on homology with other members of the TNF ligand protein superfamily, the ligand is referred to also as TNF ligand superfamily member 12 [ TNFSF12 ]. TWEAK induces IL-8 synthesis in a number of cell lines. TWEAK induces cell death by apoptosis in the human adenocarcinoma cell line HT29 in the presence of IFN-γ. It's been reported that TWEAK contributes to macrophage homeostasis by mediating CD4 (+)T-cell killing of antigen-presenting macrophages. It's been reported that TWEAK plays a role in brain inflammation . Human astrocytes derived from different regions of the brain specifically bind TWEAK and are resistant to apoptosis mediated by TWEAK. TWEAK induces the production of large amounts of IL-8 and IL-6 in astrocytes and significantly increases the expression of ICAM-1. The TWEAK receptor has been cloned from a human umbilical vein endothelial cell library. The short cytoplasmic domain of this receptor binds TRAF-1 , TRAF-2 , and TRAF-3. Cross-linking of this receptor induces growth of human umbilical vein endothelial cells. The soluble receptor has been shown to inhibit endothelial cell migration in vitro and corneal angiogenesis in vivo.
