Suppression of NF-kappaB activation in normal T cells by supernatant fluid from human renal cell carcinomas.
T lymphocytes from patients with renal cell carcinoma (RCC) show reduced immune function and impaired activation of the transcription factor, NF-kappaB. We determined the mechanism of NF-kappaB suppression in T cells of RCC patient and determined whether supernatant fluid from RCC explants (RCC-S) induced the same phenotype of NF-kappaB suppression in normal T cells that is observed in patient T cells. The pattern of kappaB-binding activity in T cells of RCC patient was altered as compared to that seen in T cells obtained from normal volunteers. In some patients, no activation of RelA/NFkappaB1-binding activity was detectable, while in others kappaB-binding activity was modestly induced but the duration was reduced. IkappaBalpha was degraded normally following stimulation in both normal controls and T cells from RCC patients. RCC-S did not alter the cytoplasmic levels of RelA and NF-kappaB1 but did suppress their nuclear localization and inhibited the activation of RelA/NF-kappaB1 binding complexes. These results show that RCC-S can induce in normal T cells the same phenotype of impaired NF-kappaB activation that is detected in T cells of RCC patient. It also appears that NF-kappaB suppression by RCC-S may contribute to the immunosuppression of host immunity.
Department of Urology, Institute for Medical Science, Chonbuk National University Medical School, Chonju, Korea. hjkim@moak.chonbuk.ac.kr
H J
HJ
Kim
J K
JK
Park
Y G
YG
Kim
D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000378:metabolism; D046508:Culture Techniques; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D006801:Humans; D020672:I-kappa B Proteins; D007680:Kidney Neoplasms / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000096:biosynthesis / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D020569:Proto-Oncogene Proteins c-rel; D013601:T-Lymphocytes / Q000378:metabolism*; D051996:Transcription Factor RelA
D017077:Culture Media, Conditioned; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha