Induction and regulation of NFkappaB during aging: role of protein kinases.
Aging is accompanied by significant declines in immune function. To understand the basis for this age-related decline we have investigated the induction and regulation of transcription factor NFkappaB in murine T cells. We report that anti-CD3 treatment of T lymphocytes from old mice resulted in significantly lower levels of NFkappaB than those observed in similarly treated T cells from young mice. Pretreatment of T cells with staurosporine reduced the induction of NFkappaB in anti-CD3-activated cells from young mice but had no effect in similarly treated T cells from old mice. However, pretreatment with H-89 had little or no effect on the induction of NFkappaB in T cells from young mice, but significantly enhanced the induction of NFkappaB in T cells from old mice. These results suggest that the impairment in the generation of NFkappaB during aging may reflect age-associated differences in the regulation of protein kinase A.
Trebilcock
G U
GU
Department of Microbiology, Medical Genetics and Immunology, University of Kansas Medical Center, Kansas City, 66103, U/sa.
Ponnappan
U
U
D000375:Aging; D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D004306:Dose-Response Relationship, Immunologic; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D051841:Transcription Factor RelB; D014157:Transcription Factors
D017252:CD3 Complex; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; C497594:Relb protein, mouse; D014157:Transcription Factors; D051841:Transcription Factor RelB; D017868:Cyclic AMP-Dependent Protein Kinases