Tumor necrosis factor-related apoptosis-inducing ligand promotes microvascular endothelial cell hyperpermeability through phosphatidylinositol 3-kinase pathway

Hayden W. Stagg, Kanika Bowen-Jallow, Devendra A. Sawant, Miguel Rodriguez, Binu Tharakan, Ed W. Childs

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: Microvascular hyperpermeability that occurs in hemorrhagic shock and burn trauma is regulated by the apoptotic signaling pathway. We hypothesized that tumor necrosis factor-α (TNF-α)-related apoptosis-inducing ligand (TRAIL) would promote hyperpermeability directly or by interacting with other signaling pathways. Methods: Rat lung microvascular endothelial cells (RLMECs) grown on Transwell membranes (Corning Life Sciences, Lowell, MA) were treated with recombinant human TRAIL (10, 50, and 100 ng/mL) for 6 hours or TRAIL (100 ng/mL) + LY294002 (a PI3K inhibitor; 20 μmol/L), Z-DEVD-FMK (a caspase-3 inhibitor; 10 μmol/L), or the inhibitors alone. Fluorescein isothiocyanate (FITC)-albumin flux was an indicator of permeability. Caspase-3 activity was measured fluorometrically. Adherens junction integrity was studied using β-catenin immunofluorescence. Results: TRAIL + LY294002, but not TRAIL alone, induced monolayer hyperpermeability (P <.05), and caspase-3 activity (P

Original languageEnglish (US)
Pages (from-to)419-425
Number of pages7
JournalAmerican Journal of Surgery
Volume205
Issue number4
DOIs
StatePublished - Apr 2013
Externally publishedYes

Fingerprint

TNF-Related Apoptosis-Inducing Ligand
Phosphatidylinositol 3-Kinase
Endothelial Cells
Tumor Necrosis Factor-alpha
Caspase 3
Apoptosis
Ligands
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Adherens Junctions
Catenins
Caspase Inhibitors
Hemorrhagic Shock
Biological Science Disciplines
Fluorescein
Phosphatidylinositol 3-Kinases
Fluorescent Antibody Technique
Albumins
Permeability
Lung
Membranes

Keywords

  • Apoptotic signaling
  • PI3K
  • TRAIL
  • Vascular permeability

ASJC Scopus subject areas

  • Surgery

Cite this

Tumor necrosis factor-related apoptosis-inducing ligand promotes microvascular endothelial cell hyperpermeability through phosphatidylinositol 3-kinase pathway. / Stagg, Hayden W.; Bowen-Jallow, Kanika; Sawant, Devendra A.; Rodriguez, Miguel; Tharakan, Binu; Childs, Ed W.

In: American Journal of Surgery, Vol. 205, No. 4, 04.2013, p. 419-425.

Research output: Contribution to journalArticle

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AU - Rodriguez, Miguel

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AU - Childs, Ed W.

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