期刊
ANNALS OF THORACIC SURGERY
卷 96, 期 1, 页码 155-162出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.athoracsur.2013.04.013
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资金
- NHLBI NIH HHS [R01 HL106582, R01 HL106582-01] Funding Source: Medline
Background. Mechanisms of inflammation have been implicated in the pathogenesis of aortic stenosis. When stimulated, human aortic valve interstitial cells (AVICs) have been shown to become inflammatory cells. Increased levels of interleukin (IL)-1 beta have been found in the leaflets of stenotic aortic valves. The purpose of this study was to determine the effects of IL-1 beta on isolated human AVICs and to determine the intracellular signaling pathway by which the effects are mediated. The results of this study demonstrated that IL-1 beta induces an inflammatory phenotype in human AVICs. Methods. Human AVICs were isolated from normal aortic valves from explanted hearts of patients undergoing cardiac transplantation (n = 4) and grown in culture. When grown to confluence, the cells were treated with IL1 beta (10 ng/mL). Cell culture media was analyzed for IL-6, IL-8, and monocyte chemoattractant protein-1 (enzyme-linked immunosorbent assay). Cell lysates were analyzed for intercellular adhesion molecule-1 (immunoblot). Inhibition of nuclear factor-kappa beta was by Bay 11-7085 (5 mM). Inhibition of extracellular signal regulated kinase-1/2 was by PD098059 (20 nM). Statistics were by analysis of variance, with p less than 0.05 significant. Results. Interluekin-1 beta induced an inflammatory phenotype in human AVICs. The IL-1 beta stimulation resulted in significantly increased production of the inflammatory cytokines, IL-6 and IL-8, the chemokine monocyte chemoattractant protein-1, and intercellular adhesion molecule-1. Inhibition of nuclear factor-kappa beta prevented these changes, whereas inhibition of extracellular signal regulated kinase-1/2 had no effect. Conclusions. Interleukin-1 beta induced an inflammatory phenotype in human AVICs, which was prevented by inhibition of nuclear factor-kappa beta. These data implicate IL-1 beta in the pathogenesis of aortic stenosis. (C) 2013 by The Society of Thoracic Surgeons
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