Our recent studies indicate increased dexamethasone-induced programmed ce!i death (PCD) occurs in calorie restricted mice. These mice are also known to have elevated glucocorticoid levels. Since circadian based higher secretion occurs before the onset of darkness, the present study was designed to compare the circadian effect on PCD in spleen and thymus cells. Six month old ICR mice were maintained in two chambers for two months on the two lighting regimens. Lights were on from: 1) 06:00-18:00 hours; and 2) 23:00-11:00 hours. Mice from both rooms were simultaneously sacrificed at 9 AM. and PCD in spleen and thymus cells was measured by both flow cytometry analysis of cells stained with propidium iodide (PI), and DXA ladder formation analysis in cultured cells, with and without Dexarnethasone treatment for 18 hours in vitro. The results indicate a significantly higher rate of PCD in mice on a 4 PM circadian phase when compared to 9 AM. both in spleen and thymus cells (p<0.05). as measured by PI staining FACS analysis, and DNA fragmentation. PI positive thymus cells from 9 AM: 61%: 4 PM 74%: spleen 48% versus 57%. Also, cell surface Fas antigen was higher in 4 PM mice. Additionally. CD4+CD8+ thymocytes were higher indicating higher circadian corticosteroid activity influencing both positive and negative selection of T cells in the thymus. In conclusion, circadian dependent corticosteroid activity may contribute to ihe increased positive/negative selection of T cells by regulating PCD within thymus and splenic cells.
|Original language||English (US)|
|State||Published - Dec 1 1996|
ASJC Scopus subject areas
- Molecular Biology