title: Interleukin-1 Beta induces an inflammatory phenotype in human aortic valve interstitial cells through nuclear factor kappa Beta.
abstract: 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)-1β have been found in the leaflets of stenotic aortic valves. The purpose of this study was to determine the effects of IL-1β 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-1β 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 IL-1β (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-κβ was by Bay 11-7085 (5 μM). 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-1β induced an inflammatory phenotype in human AVICs. The IL-1β 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-κβ prevented these changes, whereas inhibition of extracellular signal regulated kinase-1/2 had no effect.
  
  
  CONCLUSIONS
  Interleukin-1β induced an inflammatory phenotype in human AVICs, which was prevented by inhibition of nuclear factor-κβ. These data implicate IL-1β in the pathogenesis of aortic stenosis.
authors.affiliation: Division of Cardiothoracic Surgery, University of Colorado School of Medicine, Aurora, Colorado 80045, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Nadlonek
authors.forename: Joon H
authors.initials: JH
authors.lastname: Lee
authors.forename: T Brett
authors.initials: TB
authors.lastname: Reece
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Weyant
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Cleveland
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Meng
authors.forename: David A
authors.initials: DA
authors.lastname: Fullerton
mesh_terms: D000328:Adult; D001021:Aortic Valve / Q000378:metabolism / Q000473:pathology*; D001024:Aortic Valve Stenosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D010641:Phenotype; D015398:Signal Transduction; D055815:Young Adult
chemical_list: D053583:Interleukin-1beta; D016328:NF-kappa B