Restraint stress induces lymphocyte reduction through p53 and PI3K/NF-kappaB pathways.
Restraint stress, either physical or psychological, can modulate immune function. However, the mechanisms associated with stress-induced lymphocyte reduction remains to be elucidated. We have previously shown that chronic stress induces Fas-mediated lymphocyte reduction. Here, we investigated the mechanisms by which restraint stress modulates lymphocyte reduction. Our data have shown that inhibition of p53 by the p53 inhibitor PFT-alpha attenuates stress-induced reduction in lymphocyte numbers. These results were verified using p53 knockout mice, suggesting a pivotal role of p53 in this process. In addition our data have indicated that PI3K/nuclear factor kappa B (NF-kappaB) signaling pathway plays an important role in the stress-induced lymphocyte reduction. Our study thus demonstrates that restraint stress promotes lymphocyte reduction through p53 and PI3K/NF-kappaB pathways.
Zhang
Yi
Y
Department of Internal Medicine, College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.
Foster
Robert
R
Sun
Xiuli
X
Yin
Qiaoqiao
Q
Li
Yi
Y
Hanley
Gregory
G
Stuart
Charles
C
Gan
Yili
Y
Li
Chuanfu
C
Zhang
Zhiyong
Z
Yin
Deling
D
D000704:Analysis of Variance; D000818:Animals; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D012149:Restraint, Physical / Q000379:methods; D015398:Signal Transduction / Q000502:physiology*; D013312:Stress, Physiological; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000378:metabolism*
D004791:Enzyme Inhibitors; D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53; D019869:Phosphatidylinositol 3-Kinases