During fiscal year 2011, we accomplished the following: 1. Continued analysis of BLSA 2 year returnees using the scheme established for the first round of volunteers. Specifically, this involves analysis of protein and RNA in 4 samples per volunteer: 1) unactivated cells incubated at 37C, 2,3) cells activated with anti-CD3 for 2h and 4h, and 4) unactivated cells kept at 4C (to preserve in vivo signature of gene expression). 2. Completed analysis of preparative 2D protein expression assays in young and old. 3. Compared gene expression in CD4+T cells incubated at 37 C in normal medium (containing fetal calf serum) or defined synthetic medium (lacking fetal calf serum). We found that the NF-κB-induced pathway was up-regulated and the BCR-activation pathway was down-regulated in the synthetic medium as previously noted in normal medium. One difference was that the NF-κB-induced pathway was not at the top of the list of up-regulated pathways in the synthetic medium. Thus, NFκB target genes are up-regulated by a cell-intrinsic mechanism upon metabolic activation by incubation at 37C. However, components in fetal calf serum may accentuate NF-κB up-regulation in normal serum. 4. We initiated collaborative studies with Dr. Sam John and Gordon Hager (NCI) to examine the effects of anti-inflammatory corticosteroids on human B cells. Conditions for dexamethasone treatment and chromatin immunoprecipitation studies were first standardized using the Burkitt lymphoma cell line, BJAB. Additionally, we standardized procedures to purify nave and memory primary human B cells from apheresis packs.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000386-05
Application #
8335851
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2011
Total Cost
$54,628
Indirect Cost
Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
Zip Code
Bektas, Arsun; Schurman, Shepherd H; Sen, Ranjan et al. (2017) Human T cell immunosenescence and inflammation in aging. J Leukoc Biol :
Bektas, Arsun; Sen, Ranjan; Ferrucci, Luigi (2016) Does a bit of alcohol turn off inflammation and improve health? Age Ageing :
Bektas, Arsun; Zhang, Yongqing; Lehmann, Elin et al. (2014) Age-associated changes in basal NF-?B function in human CD4+ T lymphocytes via dysregulation of PI3 kinase. Aging (Albany NY) 6:957-74
Bektas, Arsun; Zhang, Yongqing; Wood 3rd, William H et al. (2013) Age-associated alterations in inducible gene transcription in human CD4+ T lymphocytes. Aging (Albany NY) 5:18-36
Munk, Rachel B; Sugiyama, Katsuki; Ghosh, Paritosh et al. (2011) Antigen-independent IFN-? production by human naïve CD4 T cells activated by IL-12 plus IL-18. PLoS One 6:e18553
Kaileh, Mary; Sen, Ranjan (2010) Role of NF-kappaB in the anti-inflammatory effects of tocotrienols. J Am Coll Nutr 29:334S-339S