Tobacco smoke cooperates with interleukin-1β to alter β-catenin trafficking in vascular endothelium resulting in increased permeability and induction of cyclooxygenase-2 expression in vitro and in vivo

Silvia S. Barbieri, Babette B. Weksler

Research output: Contribution to journalArticle

Abstract

Cigarette smoking affects all phases of atherosclerosis from endothelial dysfunction to acute occlusive clinical events. We explored activation by exposure to tobacco smoke of two genes, β-catenin and COX-2, that play key roles in inflammation and vascular remodeling events. Using both in vivo and in vitro smoke exposure, we determined that tobacco smoke (TS) induced nuclear β-catenin accumulation and COX-2 expression and activity and moreover interacted with IL-1β to enhance these effects. Exposure of cardiac endothelial cells to tobacco smoke plus IL-1β (TS/IL-1β) enhanced permeability of endothelial monolayers and disrupted membrane VE-cadherin/β-catenin complexes, decreased β-catenin phosphorylation, and increased phosphorylation of GSK-3β, Akt, and EGFR. Transfection of endothelial cells with β-catenin-directed small interferring RNA (siRNA) suppressed TS/IL-1β-mediated effects on COX-2 modulation. Inhibitors of EGFR and phosphatidylinositol-3-kinase also abolished both the TS/IL-1β-mediated modulation of the Akt/GSK-3β/β-catenin pathway and enhancement of COX-2 expression. Moreover, increased levels of Akt and GSK-3β phosphorylation, nuclear β-catenin accumulation, COX-2 expression, and IL-1β were observed in cardiovascular tissue of ApoE-/- mice exposed to cigarette smoke daily for 2 wk. Our results suggest a novel mechanism by which cigarette smoking can induce proinflammatory and proatherosclerotic effects in vascular tissue.

Original languageEnglish
Pages (from-to)1831-1843
Number of pages13
JournalFASEB Journal
Volume21
Issue number8
DOIs
Publication statusPublished - Jun 2007

Keywords

  • Endothelial cells
  • Inflammation
  • Signal transduction

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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