title: Interleukin-7 induces recruitment of monocytes/macrophages to endothelium.
abstract: OBJECTIVE
  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.
  
  
  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-κB; (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).
  
  
  CONCLUSIONS
  These results suggest that IL-7 inflames endothelium via PI3K/AKT-dependent and -independent activation of NF-κB and recruits monocytes/macrophages to the endothelium, thus playing an active role in atherogenesis.
authors.affiliation: Department of Medicine,  Baylor College of Medicine, Houston, TX,  USA.
authors.forename: Rongying
authors.initials: R
authors.lastname: Li
authors.forename: Antoni
authors.initials: A
authors.lastname: Paul
authors.forename: Kerry W S
authors.initials: KW
authors.lastname: Ko
authors.forename: Michael
authors.initials: M
authors.lastname: Sheldon
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Rich
authors.forename: Tomoya
authors.initials: T
authors.lastname: Terashima
authors.forename: Carrie
authors.initials: C
authors.lastname: Dieker
authors.forename: Shelley
authors.initials: S
authors.lastname: Cormier
authors.forename: Lan
authors.initials: L
authors.lastname: Li
authors.forename: Elie A
authors.initials: EA
authors.lastname: Nour
authors.forename: Lawrence
authors.initials: L
authors.lastname: Chan
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Oka
mesh_terms: D000256:Adenoviridae; D000818:Animals; D001013:Aorta, Thoracic; D053318:Apolipoprotein E3 / Q000235:genetics; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D020869:Gene Expression Profiling; D005822:Genetic Vectors; D015851:Interleukin-7 / Q000494:pharmacology* / Q000502:physiology; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D053318:Apolipoprotein E3; D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D015851:Interleukin-7; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases