Evidence for lowered induction of nuclear factor kappa B in activated human T lymphocytes during aging

被引:60
作者
Trebilcock, GU
Ponnappan, U
机构
[1] JOHN L MCCLELLAN MEM HOSP, VET AFFAIRS MED RES, GRECC, LITTLE ROCK, AR 72205 USA
[2] UNIV ARKANSAS MED SCI HOSP, DEPT MED, LITTLE ROCK, AR 72205 USA
[3] UNIV ARKANSAS MED SCI HOSP, DEPT IMMUNOL & MICROBIOL, LITTLE ROCK, AR 72205 USA
关键词
aging; nuclear factor kappa B; inhibitor kappa B; anti-CD3; phorbol myristate acetate; tumor necrosis factor-alpha;
D O I
10.1159/000213785
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Transcription factor NF kappa B (nuclear factor kappa B) is induced in T lymphocytes from young individuals following activation with a variety of stimuli including anti-CD3, phorbol myristate acetate (PMA), and tumor necrosis factor-alpha (TNF-alpha). In contrast, activated T lymphocytes from older individuals show a significant reduction in the induction of NF kappa B in response to the same stimuli. The age-related decline in induction of NF kappa B could not be attributed to alteration in the composition of subunits, p50 and p65 were found to be the predominant subunits of induced NF kappa B in T cells from young as well as elderly donors. Furthermore, similar levels of NF kappa B were found in the cytosols of unactivated T cells from both young and elderly donors suggesting that precursor levels of NF kappa B remain unaltered during aging. These results suggest that an age-associated decline in the induction of NF kappa B in activated T cells from elderly individuals may be attributable to altered regulation of the inhibitor, I kappa B, and may play an important role in immune dysregulation accompanying aging.
引用
收藏
页码:137 / 146
页数:10
相关论文
共 32 条
[1]  
BAEUERLE PA, 1994, ANNU REV IMMUNOL, V12, P141, DOI 10.1146/annurev.immunol.12.1.141
[2]  
BEAUPARLANT P, 1994, ONCOGENE, V9, P3189
[3]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[4]   INTERLEUKIN-2, INTERLEUKIN-2 RECEPTOR, AND INTERFERON-GAMMA SYNTHESIS AND MESSENGER-RNA EXPRESSION IN PHORBOL-MYRISTATE ACETATE AND CALCIUM IONOPHORE A23187-STIMULATED T-CELLS FROM ELDERLY HUMANS [J].
CHOPRA, RK ;
HOLBROOK, NJ ;
POWERS, DC ;
MCCOY, MT ;
ADLER, WH ;
NAGEL, JE .
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY, 1989, 53 (02) :297-308
[5]  
Davis LG., 1986, Basic Methods in Molecular Biology
[6]   ACCURATE TRANSCRIPTION INITIATION BY RNA POLYMERASE-II IN A SOLUBLE EXTRACT FROM ISOLATED MAMMALIAN NUCLEI [J].
DIGNAM, JD ;
LEBOVITZ, RM ;
ROEDER, RG .
NUCLEIC ACIDS RESEARCH, 1983, 11 (05) :1475-1489
[7]  
GRILLI M, 1993, INT REV CYTOL, V143, P1
[8]  
GUPTA S, 1989, ANN NY ACAD SCI, V568, P277
[9]   RAPID PROTEOLYSIS OF I-KAPPA-B-ALPHA IS NECESSARY FOR ACTIVATION OF TRANSCRIPTION FACTOR NF-KAPPA-B [J].
HENKEL, T ;
MACHLEIDT, T ;
ALKALAY, I ;
KRONKE, M ;
BEN-NERIAH, Y ;
BAEUERLE, PA .
NATURE, 1993, 365 (6442) :182-185
[10]   KAPPA-B SPECIFIC DNA-BINDING PROTEINS - ROLE IN THE REGULATION OF HUMAN INTERLEUKIN-2 GENE-EXPRESSION [J].
HOYOS, B ;
BALLARD, DW ;
BOHNLEIN, E ;
SIEKEVITZ, M ;
GREENE, WC .
SCIENCE, 1989, 244 (4903) :457-460