Age-associated changes in basal NF-?B function in human CD4+ T lymphocytes via dysregulation of PI3 kinase.

ABSTRACT: 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-?B is higher in purified and rested human CD4+ T lymphocytes from older compared to younger individuals. This increase of NF-?B -associated transcription includes transcripts for pro-inflammatory cytokines such as IL-1 and chemokines such as CCL2 and CXCL10. We demonstrate that NF-?B 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-?B activity may contribute to the mild pro-inflammatory state of aging.

SUBMITTER: Bektas A 

PROVIDER: S-EPMC4276789 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature