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Poly(I:C)-induced adhesion molecule expression mediated by NF-{kappa}B and phosphoinositide 3-kinase-Akt signaling

Tomoko Orita1, Kazuhiro Kimura, Hong-Yan Zhou

  • 1Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.

Investigative Ophthalmology & Visual Science
|June 25, 2010
PubMed
Abstract

Insights

Polyinosinic-polycytidylic acid [poly(I:C)] upregulates VCAM-1 and ICAM-1 in corneal fibroblasts by activating nuclear factor-kappa B (NF-κB) and phosphoinositide 3-kinase (PI3K)-Akt pathways. These signaling cascades are crucial for immune responses in viral stromal keratitis.

Area of Science:

  • Ophthalmology
  • Immunology
  • Cell Biology

Background:

  • Viral infections of the eye can cause chronic stromal keratitis.
  • Polyinosinic-polycytidylic acid [poly(I:C)], a viral RNA analog, stimulates adhesion molecule expression in corneal cells.

Purpose of the Study:

  • To investigate the roles of nuclear factor-kappa B (NF-κB) and phosphoinositide 3-kinase (PI3K)-Akt signaling in poly(I:C)-induced adhesion molecule expression.
  • To understand the molecular mechanisms underlying viral-induced inflammation in the corneal stroma.

Main Methods:

  • Human corneal fibroblasts were treated with poly(I:C) and inhibitors of NF-κB (IκB kinase 2 inhibitor) and PI3K (LY294002).
  • Expression of VCAM-1, ICAM-1, ICAM-2, and E-selectin was analyzed using immunoblotting.
  • Phosphorylation of IκB-α and Akt was assessed, along with subcellular localization of adhesion molecules via immunofluorescence.

Main Results:

  • Poly(I:C) significantly increased VCAM-1 and ICAM-1 expression, but not ICAM-2 or E-selectin.
  • Poly(I:C) induced phosphorylation of IκB-α and Akt.
  • Inhibition of both NF-κB and PI3K pathways reduced poly(I:C)-induced VCAM-1 and ICAM-1 expression.

Conclusions:

  • NF-κB and PI3K-Akt signaling pathways are essential mediators of poly(I:C)-induced VCAM-1 and ICAM-1 upregulation in corneal fibroblasts.
  • The PI3K pathway acts upstream of NF-κB activation.
  • These pathways are critical in regulating immune and inflammatory responses to ocular viral infections.

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