TY - JOUR
T1 - Effect of nuclear factor κB inhibition on tumor cell sensitivity to natural killer-mediated cytolytic function
AU - Mami-Chouaib, Fathia
AU - Ameyar, Maya
AU - Dorothée, Guillaume
AU - Bentires-Alj, Mohamed
AU - Dziembowska, Magdalena
AU - Delhalle, Silvie
AU - Gay, Françoise
AU - Stancou, Rodica
AU - Bours, Vincent
AU - Chouaib, Salem
PY - 2001
Y1 - 2001
N2 - Inhibition of the transcription factor NF-κB has been reported to increase cell sensitivity to TNF and some cytotoxic drugs. We investigated the effect of NK-κB inhibition on the susceptibility of tumor cells to freshly isolated, nonactivated, human NK cells and to a TCRγ/δ T cell clone displaying an MHC-unrestricted "NK-like" lysis. Using electrophoretic mobility shift assay, we first demonstrated that NF-κB/DNA binding activity was induced in target cells following coculture with NK cells or TCRγ/δ T cell clone. To investigate the effect of target cell NF-κB inhibition on NK-mediated lysis, we blocked NF-κB translocation by introducting a human cDNA coding for a mutated IκB-α. Interestingly, our results indicated that inhibition of NF-κB did not induce any increase in either granzyme-dependent non-MHC-restricted cytotoxicity mediated by fresh non-stimulated NK cells and by TCR γ/δ T cell clone or in CD95-mediated lysis. These results emphasize that NF-κB expressed in target cells does not play a role in the molecular process related to the control of target cell susceptibility to NK-mediated lysis and suggest that the NF-κB pathway is not a general mechanism for controlling the cytotoxic response.
AB - Inhibition of the transcription factor NF-κB has been reported to increase cell sensitivity to TNF and some cytotoxic drugs. We investigated the effect of NK-κB inhibition on the susceptibility of tumor cells to freshly isolated, nonactivated, human NK cells and to a TCRγ/δ T cell clone displaying an MHC-unrestricted "NK-like" lysis. Using electrophoretic mobility shift assay, we first demonstrated that NF-κB/DNA binding activity was induced in target cells following coculture with NK cells or TCRγ/δ T cell clone. To investigate the effect of target cell NF-κB inhibition on NK-mediated lysis, we blocked NF-κB translocation by introducting a human cDNA coding for a mutated IκB-α. Interestingly, our results indicated that inhibition of NF-κB did not induce any increase in either granzyme-dependent non-MHC-restricted cytotoxicity mediated by fresh non-stimulated NK cells and by TCR γ/δ T cell clone or in CD95-mediated lysis. These results emphasize that NF-κB expressed in target cells does not play a role in the molecular process related to the control of target cell susceptibility to NK-mediated lysis and suggest that the NF-κB pathway is not a general mechanism for controlling the cytotoxic response.
KW - Cytotoxicity
KW - Human NK cell
KW - NF-κB
UR - http://www.scopus.com/inward/record.url?scp=0035108282&partnerID=8YFLogxK
U2 - 10.1002/1521-4141(200102)31:2<433::AID-IMMU433>3.0.CO;2-T
DO - 10.1002/1521-4141(200102)31:2<433::AID-IMMU433>3.0.CO;2-T
M3 - Article
C2 - 11180107
AN - SCOPUS:0035108282
SN - 0014-2980
VL - 31
SP - 433
EP - 439
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 2
ER -