Suppression of NF-kappaB activation in normal T cells by supernatant fluid from human renal cell carcinomas.
10.3346/jkms.1999.14.3.299
- Author:
Hyung Jin KIM
1
;
Jong Kwan PARK
;
Young Gon KIM
Author Information
1. Department of Urology, Institute for Medical Science, Chonbuk National University Medical School, Chonju, Korea. hjkim@moak.chonbuk.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Transcription factors;
T-lymphocytes;
Kidney neoplasms;
Proteins, NF-kappa B
- MeSH:
Carcinoma, Renal Cell/metabolism*;
Culture Media, Conditioned/metabolism;
DNA-Binding Proteins/biosynthesis;
Human;
Kidney Neoplasms/metabolism*;
NF-kappa B/metabolism*;
NF-kappa B/biosynthesis;
Proto-Oncogene Proteins/biosynthesis;
Proto-Oncogene Proteins c-rel;
T-Lymphocytes/metabolism*;
Tissue Culture
- From:Journal of Korean Medical Science
1999;14(3):299-303
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.