Effect of nuclear factor kappa B inhibition on tumor cell sensitivity to natural killer-mediated cytolytic function

Inhibition of the transcription factor NF-kappaB has been reported to incre ase cell sensitivity to TNF and some cytotoxic drugs. We investigated the e ffect of NK-kappaB inhibition on the susceptibility of tumor cells to fresh ly isolated, nonactivated, human NK cells and to a TCR gamma/delta T cell d one displaying an MHC-unrestricted "NK-like" lysis. Using electrophoretic m obility shift assay, we first demonstrated that NF-kappaB/DNA binding activ ity was induced in target cells following coculture with NK cells or TCR ga mma/delta T cell clone. To investigate the effect of tar get cell NF-kappaB inhibition on NK-mediated lysis, we blocked NF-kappaB translocation by int roducing a human cDNA coding for a mutated I kappaB-alpha. Interestingly, o ur results indicated that inhibition of NF-kappaB did not induce any increa se in either granzyme-dependent non-MHC-restricted cytotoxicity mediated by fresh non-stimulated NK cells and by TCR gamma/delta T cell clone or in CD 95-mediated lysis. These results emphasize that NF-kappaB expressed in targ et cells does not play a role in the molecular process related to the contr ol of target cell susceptibility to NK-mediated lysis and suggest that the NF-kappaB pathway is not a general mechanism for controlling the cytotoxic response.