Expression of cytokine and apoptotic genes : a role for NF-kB in the regulation of TNF- related apoptosis inducing ligand (TRAIL) expression

The NF-kappaB family of transcription factors is involved in immunoregulation, cellular differentiation and growth. Using Jurkat cells engineered to inducibly express a transdominant form of IkappaBalpha (TD-IkappaBalpha), we have found two novel genes regulated NF-kappaB transcription factor, interleukin 13 and TNF-related apoptosis-inducing ligand (TRAIL) apoptotic signaling protein. Treatment with a variety of T cell receptor mimetics resulted in a rapid and dramatic increase in the expression of TRAIL mRNA as well as cell surface protein. The induced expression of TRAIL was linked to the presence of a c-Rel binding site at position -256 to -265. Mutation of this site or an adjacent kappaB site resulted in a complete loss of inducibility of the TRAIL promoter. The regulation of TRAIL expression may represent a general mechanism that contributes to the control of TRAIL-mediated apoptosis in T lymphocytes