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-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). CONCLUSION: 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.
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-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). CONCLUSION: 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: Erin D MacDougall; Farah Kramer; Patti Polinsky; Shelley Barnhart; Bardia Askari; Fredrik Johansson; Rebecca Varon; Michael E Rosenfeld; Kazuhiro Oka; Lawrence Chan; Stephen M Schwartz; Karin E Bornfeldt Journal: Am J Pathol Date: 2006-06 Impact factor: 4.307
Authors: Joel A G van Roon; Marieke C Verweij; Marion Wenting-van Wijk; Kim M G Jacobs; Johannes W J Bijlsma; Floris P J G Lafeber Journal: Arthritis Rheum Date: 2005-06
Authors: Antonio Ferrante; Brenton S Robinson; Harmeet Singh; Hubertus P A Jersmann; Judith V Ferrante; Zhi H Huang; Neil A Trout; Michael J Pitt; Deborah A Rathjen; Christopher J Easton; Alf Poulos; Rolf H Prager; Frank S Lee; Charles S T Hii Journal: Circ Res Date: 2006-06-08 Impact factor: 17.367
Authors: Eugene Trogan; Jonathan E Feig; Snjezana Dogan; George H Rothblat; Véronique Angeli; Frank Tacke; Gwendalyn J Randolph; Edward A Fisher Journal: Proc Natl Acad Sci U S A Date: 2006-03-01 Impact factor: 11.205
Authors: C Romano Carratelli; I Nuzzo; D Cozzolino; C Bentivoglio; R Paolillo; A Rizzo Journal: Int Immunopharmacol Date: 2005-11-28 Impact factor: 4.932
Authors: Parul Rai; Vijaya M Joshi; Jason F Goldberg; Amber M Yates; Victoria I Okhomina; Rhiannon Penkert; Kenneth I Ataga; Guolian Kang; Jane S Hankins Journal: Blood Adv Date: 2021-01-12