Decreased c-rel activation contributes to aberrant interleukin-2 expression in CD4(+)T cells of aged rats.
Studies indicated significantly decreased expression of interleukin-2 (IL-2) with age. This decrease could be a major contributory factor to the increased frequency of morbidity and mortality among the elderly. C-rel is a key coregulator of IL-2 expression. However, it is unknown whether aging inhibits normal c-rel activation, thereby decreasing production of IL-2. We analyzed the dynamics of IL-2 expression in CD4(+)T cells from different aged rats (young group: around 6 months (n=6), aged group: around 24 months (n=6)). The expression of the CD3 receptor and CD28 receptor in the CD4(+)T cells was assessed by flow cytometry. Translocation of c-rel and its protein level in the cytoplasm and nucleus at different time points were detected by confocal microscopy and Western blotting. Chromatin immunoprecipitation (ChIP) was used to analyze the status of c-rel binding to the IL-2 promoter region in the different aged rats. Our results showed the CD4(+)T cells from young rats and aged rats showed different expression kinetics of IL-2 after stimulation. The expression level of IL-2 was higher in young rats compared with aged rats at 24h and 48h. Data showed lower CD3 receptor expression on CD4(+)T cells from aged rats compared with young rats. Although the CD28 receptors declined on the aged CD4(+)T cells, the difference was not significant. After stimulation for 0.5h, more c-rel was translocated into nucleus markedly compared with that in the aged group. ChIP showed that in aged CD4(+)T cells, c-rel DNA binding was inhabited compared with that in young cells. Therefore, reduced IL-2 production in activated CD4(+)T cells from aged rats is associated with concomitant impairments in the activation of c-rel.
Department of Biochemistry, College of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China.
Zhangbin
Z
Gong
Shanghai Geriatric Institute of Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, PR China.
Te
T
Liu
Shanghai Research Center for Model Organisms, Shanghai 201203, PR China.
Yinhan
Y
Wan
Department of Biochemistry, College of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China.
Zhifeng
Z
Hang
Department of Medicine, Tibet University for Nationalities, Xianyang 712082, PR China; Spinal Cord and Brain Injury Research Center, College of Medicine, University of Kentucky, Lexington, KY 40536, USA.
Xiaopeng
X
Tong
Spinal Cord and Brain Injury Research Center, College of Medicine, University of Kentucky, Lexington, KY 40536, USA.
Bei
B
Zhang
Medical Sciences Research Center, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201203, PR China.
Haozheng
H
Yang
Department of Biochemistry, College of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China.
Xueli
X
Zhang
Department of Biochemistry, College of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China.
Lina
L
Zhang
Department of Biochemistry, College of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China. Electronic address: jinguoqin8405@126.com.
Guoqin
G
Jin
D021581:Active Transport, Cell Nucleus; D000367:Age Factors; D000375:Aging / Q000235:genetics / Q000276:immunology*; D000818:Animals; D015153:Blotting, Western; D018106:CD28 Antigens / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D020569:Proto-Oncogene Proteins c-rel / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018106:CD28 Antigens; D017252:CD3 Complex; D007376:Interleukin-2; D020569:Proto-Oncogene Proteins c-rel
Aging; C-rel; Immunosenescence; Interleukin-2; Transcription