TNF-alpha (Tumor necrosis factor alpha) plays a central role in inflammation, immune system development, apoptosis, and lipid metabolism. It is produced by a wide variety of immune, epithelial, endothelial, and tumor cells. Cell surface trimeric TNF-alpha can induce the lysis of neighboring tumor cells and virus infected cells. Shedding of membrane bound TNF-alpha by TACE (ADAM17) releases the bioactive cytokine. TNF-alpha binds TNF RI and TNF RII and induces apoptotic signaling through the death domain of TNF RI.