May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Angptl4 Suppresses TNF- Stimulated Monocyte Adhesion to Endothelial Cells by Modulation of NFB Signaling
Author Affiliations & Notes
  • Y. Ito
    Angiogenesis Labo, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
    Ophthalmology and Visual Science, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
  • S. Nakao
    Angiogenesis Labo, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
  • T. Hisatomi
    Angiogenesis Labo, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
  • K. Noda
    Angiogenesis Labo, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
  • H. Tanihara
    Ophthalmology and Visual Science, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
  • A. Hafezi-Moghadam
    Angiogenesis Labo, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
  • J. W. Miller
    Angiogenesis Labo, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
  • E. S. Gragoudas
    Angiogenesis Labo, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
  • I. K. Kim
    Angiogenesis Labo, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  Y. Ito, None; S. Nakao, None; T. Hisatomi, None; K. Noda, None; H. Tanihara, None; A. Hafezi-Moghadam, None; J.W. Miller, None; E.S. Gragoudas, None; I.K. Kim, None.
  • Footnotes
    Support  MEEI /Bausch and Lomb Japan Vitreoretinal Research Fellowship
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 3895. doi:https://doi.org/
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    • Get Citation

      Y. Ito, S. Nakao, T. Hisatomi, K. Noda, H. Tanihara, A. Hafezi-Moghadam, J. W. Miller, E. S. Gragoudas, I. K. Kim; Angptl4 Suppresses TNF- Stimulated Monocyte Adhesion to Endothelial Cells by Modulation of NFB Signaling. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3895. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Angiopoietin-like protein 4 (Angptl4) is a 70kD secreted glycoprotein, and a downstream target of the peroxisome proliferators-activated receptors alpha (PPARα) and gamma (PPARγ), which affect angiogenesis, metabolism, and inflammation. Previously, we reported that Angptl4 suppressed angiogenesis in the corneal micropocket assay and tumor xenograft model. In this study, we investigate the effect of Angptl4 in tumor necrosis factor alpha (TNF-α)-induced expression of adhesion molecules in endothelial cells.

Methods: : Human umbilical vein endothelial cells (HUVECs) at P4~7 were cultured with TNF-α (1 ng/ml) and angptl4 (0~3 µg/ml), and cellular proteins were extracted. Western blotting analysis was performed for intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), nuclear factor-ΚB (NFΚB), and phospho-NFΚB. Monocyte-endothelial cell adhesion assays were performed using HUVECs and DiI-labeled human monocytic U937 cells. After HUVECs were stimulated with TNF-α and angptl4 for 6 hours, DiI-labeled U937 cells were added with continued incubation for 1 hour. Non-adherent cells were removed by washing three times with pre-warmed PBS and monocytes adherent to HUVECs were counted.

Results: : TNF-α alone increased ICAM-1 and VCAM-1 protein levels in HUVECs after 6 hours; however, addition of Angptl4 suppressed ICAM-1 and VCAM-1 protein levels dose-dependently in western blot analysis. Moreover, Angptl4 reduced TNF-α-stimulated phospho-NFΚB protein induction as detected by western blot analysis. Monocyte-endothelial cell adhesion assays demonstrated that addition of Angptl4 reduced the adhesion of U937 to TNF-α-stimulated HUVECs.

Conclusions: : TNF-α-induced recruitment of monocytes may play an important role in the pathophysiology of ocular inflammatory disease. Our data suggest that Angptl4 suppresses monocyte adhesion to TNF-α-stimulated HUVECs by modulating NFΚB signaling. Therefore, Angptl4 represents an endogenously expressed protein that may have potential as a therapeutic agent for ocular inflammation.

Keywords: inflammation 
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