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Tumor Necrosis Factor-α Upregulates Angiopoietin-2 in Human Umbilical Vein Endothelial Cells

https://doi.org/10.1006/bbrc.2000.2296Get rights and content

Abstract

The angiopoietin-Tie2 system is an important regulator of vasculogenesis and vascular integrity. Angiopoietin-2 (Ang2) disrupts blood vessel formation in the developing embryo by antagonizing the effects of angiopoietin-1 (Ang1) on the Tie2 receptor. In this study, we examined the effect of a well-known proinflammatory cytokine, tumor necrosis factor-α (TNF-α), on Ang2 expression in human umbilical vein endothelial cells. Reverse transcriptase-polymerase chain reaction and Northern blot analyses indicated that TNF-α induced Ang2 mRNA expression in a time- and dose-dependent manner. Western blot analyses revealed that TNF-α treatment increased cellular Ang2 protein. TNF-α induced less Ang2 mRNA expression in the presence of nuclear factor-κB (NF-κB) inhibitor. These results suggest that TNF-α-induced inflammatory angiogenesis might be facilitated by the induction of Ang2.

References (22)

  • S. Davis et al.

    Cell

    (1996)
  • C. Suri et al.

    Cell

    (1996)
  • H. Oh et al.

    J. Biol. Chem.

    (1999)
  • A. Stratmann et al.

    Am. J. Pathol.

    (1998)
  • I. Kim et al.

    J. Biol. Chem.

    (1999)
  • M.J. Kang et al.

    J. Mol. Cell. Cardiol.

    (1997)
  • L. Schweigerer et al.

    Biochem. Biophys. Res. Commun.

    (1987)
  • M. Yoshizumi et al.

    J. Biol. Chem.

    (1992)
  • F. Bussolino et al.

    Eur. J. Cancer.

    (1996)
  • W.N. Procopio et al.

    J. Biol. Chem.

    (1999)
There are more references available in the full text version of this article.

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To whom correspondence should be addressed at National Creative Research Initiatives Center for Cardiac Regeneration, Chonbuk University School of Medicine, San 2-20, Keum-Am-Dong, Chonju, 560-180, Republic of Korea. Fax: 82-652-270-4071. E-mail: [email protected].

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