文章基本信息

标题：Age-associated changes in basal NF-κB function in human CD4⁺ T lymphocytes via dysregulation of PI3 kinase
本地全文：下载
作者：Arsun Bektas ; Yongqing Zhang ; Elin Lehmann 等
期刊名称：Aging
出版年度：2014
卷号：6
期号：11
页码：957-974
出版社：U.S.Department of Health & Human Service
摘要：Immune impairment and high circulating level of pro-inflammatory cytokines are landmarks of human aging. However, the molecular basis of immune dys-regulation and the source of inflammatory markers remain unclear. Here we demonstrate that in the absence of overt cell stimulation gene expression mediated by the transcription factor NF-κB is higher in purified and rested human CD4⁺ T lymphocytes from older compared to younger individuals. This increase of NF-κB -associated transcription includes transcripts for pro-inflammatory cytokines such as IL-1 and chemokines such as CCL2 and CXCL10. We demonstrate that NF-κB up-regulation is cell-intrinsic and mediated in part by phosphatidylinositol 3-kinase (PI3K) activity induced in response to metabolic activity, which can be moderated by rapamycin treatment. Our observations provide direct evidence that dys-regulated basal NF-κB activity may contribute to the mild pro-inflammatory state of aging.
关键词：CD4+ T cells; NF-κB; PI3K; human aging; gene expression