title: Interleukin-1beta induced vascular permeability is dependent on induction of endothelial tissue factor (TF) activity.
abstract: IL-1beta is a pleotropic cytokine that may mediate increased procoagulant activity and permeability in endothelial tissue during inflammatory conditions. The procoagulant effects of IL-1beta are mediated through induction of tissue factor (TF) but its alterations on vascular permeability are not well characterized. We found that IL-1beta induced a rapid and dose-dependent increase in TF activity in human umbilical vein endothelial cells (ECs) under routine culture conditions. However, IL-1beta caused a rapid and marked increase in permeability across confluent EC monolayers using a two-compartment in vitro model only in the presence of factor VIII-deficient plasma that was completely abrogated by neutralizing anti-TF antibody pre-treatment. In vitro permeability was associated with loss of EC surface expression of VE-cadherin and contraction of F-actin cytoskeletal elements that resulted in EC intercellular gap formation. These data demonstrate that IL-1beta induces marked changes in permeability across activated endothelium via a TF dependent mechanism and suggest that modulation of TF activity may represent a strategy to treat various acute and chronic inflammatory conditions mediated by this cytokine.
authors.affiliation: Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. markus.puhlmann@verizon.net
authors.forename: Markus
authors.initials: M
authors.lastname: Puhlmann
authors.forename: David M
authors.initials: DM
authors.lastname: Weinreich
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Farma
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Carroll
authors.forename: Ewa M
authors.initials: EM
authors.lastname: Turner
authors.forename: H Richard
authors.initials: HR
authors.lastname: Alexander