Ontology highlight
ABSTRACT: Aims
Interleukin-7 (IL-7) is a master regulator of T-cell development and homoeostasis. Increased IL-7 levels are associated with inflammatory diseases. The aims of this study were to determine whether IL-7 is a biomarker for inflammatory conditions or an active participant in atherogenesis.Methods and results
Advanced atherosclerotic lesions in Apoe(-/-) mice were regressed by long-term cholesterol lowering through treatment with a helper-dependent adenovirus expressing apolipoprotein E (n= 6-10). Using this model, gene expression patterns in the aorta were analysed at an early phase of regression by microarray. After stringent statistical analysis, we found that IL-7 expression is significantly reduced in response to lowering of cholesterol (n= 6). To understand the importance of IL-7 down-regulation for atherosclerotic regression, we studied the effects and mechanisms of action of IL-7 on endothelial cells (ECs) in vitro as well as in vivo. Our major findings are: (i) IL-7 up-regulates cell adhesion molecules and monocyte chemoattractant protein-1 in ECs and promotes monocyte adhesion to ECs; (ii) this regulation is mediated by phosphatidylinositol 3-kinase (PI3K)/AKT-dependent and -independent activation of NF-?B; (iii) elevation of plasma IL-7 induces recruitment of monocytes/macrophages to endothelium without affecting plasma cholesterol (n= 5, 6); and (4) lack of IL-7 in bone marrow-derived cells reduces migration of monocytes/macrophages to the lesions (n= 5, 6).Conclusion
These results suggest that IL-7 inflames endothelium via PI3K/AKT-dependent and -independent activation of NF-?B and recruits monocytes/macrophages to the endothelium, thus playing an active role in atherogenesis.
SUBMITTER: Li R
PROVIDER: S-EPMC3598429 | biostudies-literature | 2012 Dec
REPOSITORIES: biostudies-literature
Li Rongying R Paul Antoni A Ko Kerry W S KW Sheldon Michael M Rich Benjamin E BE Terashima Tomoya T Dieker Carrie C Cormier Shelley S Li Lan L Nour Elie A EA Chan Lawrence L Oka Kazuhiro K
European heart journal 20110730 24
<h4>Aims</h4>Interleukin-7 (IL-7) is a master regulator of T-cell development and homoeostasis. Increased IL-7 levels are associated with inflammatory diseases. The aims of this study were to determine whether IL-7 is a biomarker for inflammatory conditions or an active participant in atherogenesis.<h4>Methods and results</h4>Advanced atherosclerotic lesions in Apoe(-/-) mice were regressed by long-term cholesterol lowering through treatment with a helper-dependent adenovirus expressing apolipop ...[more]