INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1) IS SYNERGISTICALLY ACTIVATED BY TNF-ALPHA AND IFN-GAMMA RESPONSIVE SITES

Human ICAM-1 expression can be upregulated by IFN-gamma or TNF-alpha a nd is synergistically increased by a combination of both cytokines. Tr ansient transfections of ICAM-1/luciferase constructs identified two r egulatory regions mediating the cytokine responses and both were found to be necessary for synergism. Using electrophoretic mobility shift a ssays and specific antibodies we observed that the NF-kappa B like seq uence at -187 bound both p65/p50 and p65/c-Rel in the presence of TNF- alpha, while the interferon responsive region at -75 bound Stat1 alpha (p91). Treatment with IFN-gamma together with TNF-alpha did not lead to any additional or enhanced bands, suggesting that both transcriptio n factor complexes function independently to increase the transcriptio n initiation.