Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

TNF modulates endothelial properties by decreasing cAMP

S Koga1, S Morris, S Ogawa

  • 1Department of Physiology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.

The American Journal of Physiology
|May 1, 1995
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

The modern treatment of metrorrhagia.

The Medical press·2010
Same author

Trilene in labour.

British medical journal·2010
Same author

Prevention of epidemic neonatal diarrhoea.

Lancet (London, England)·2010
Same author

The Zondek-Aschheim Test after Partial Hypophysectomy: (Section of Obstetrics and Gynæcology).

Proceedings of the Royal Society of Medicine·2009
Same author

Differential effect of plasma or erythrocyte AGE-ligands of RAGE on expression of transcripts for receptor isoforms.

Diabetes & metabolism·2009
Same author

Visualization of intracerebral arteries by synchrotron radiation microangiography.

AJNR. American journal of neuroradiology·2007

Tumor necrosis factor-alpha (TNF-alpha) decreases endothelial cell barrier function by reducing intracellular cyclic adenosine monophosphate (cAMP) levels, partly through increased phosphodiesterase activity. This mechanism contributes to vascular dysfunction during sepsis.

Area of Science:

  • Cell Biology
  • Immunology
  • Vascular Biology

Background:

  • Tumor necrosis factor-alpha (TNF-alpha) is implicated in vascular dysfunction and increased permeability during sepsis.
  • Endothelial cell (EC) barrier function is crucial for maintaining vascular integrity.
  • Previous studies suggest TNF-alpha diminishes EC barrier function.

Purpose of the Study:

  • To investigate the mechanism by which TNF-alpha alters endothelial cell barrier function.
  • To determine the role of intracellular cyclic adenosine monophosphate (cAMP) in TNF-alpha-induced changes in ECs.
  • To examine the effect of TNF-alpha on phosphodiesterase (PDE) activity and thrombomodulin expression in ECs.

Main Methods:

  • Cultured bovine aortic endothelial cell (EC) monolayers were treated with TNF-alpha.

Related Experiment Videos

  • Measurements included diffusional transit of labeled molecules ([3H]sorbitol, [3H]inulin, 125I-albumin).
  • Intracellular cAMP levels, cyclic nucleotide phosphodiesterase (CNPDE) activities (PDE IV, PDE II), and thrombomodulin mRNA/activity were assessed. cAMP analogues and PDE inhibitors were used.

    • Main Results:

    • TNF-alpha increased EC permeability in a time- and dose-dependent manner, paralleled by a decrease in intracellular cAMP.
    • cAMP analogues (dibutyryl cAMP) prevented TNF-alpha-induced barrier dysfunction.
    • TNF-alpha increased PDE IV and PDE II activities, suggesting post-translational modification of PDE IV.
    • Thrombomodulin mRNA and activity were reduced by TNF-alpha and restored by cAMP analogues.

    Conclusions:

    • Activation of EC CNPDE activity and subsequent reduction in intracellular cAMP contribute to TNF-alpha-induced increases in EC permeability.
    • TNF-alpha promotes a procoagulant EC phenotype through decreased intracellular cAMP.
    • Targeting CNPDE activity or increasing cAMP levels may offer therapeutic strategies for sepsis-induced vascular dysfunction.