June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Interleukin-1β enhances cell migration through AP-1 and NF-κB pathway dependent FGF2 expression in human corneal endothelial cells
Author Affiliations & Notes
  • Daniel Sand
    Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA
  • JeongGoo Lee
    Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA
  • J Heur
    Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA
  • Footnotes
    Commercial Relationships Daniel Sand, None; JeongGoo Lee, None; J Heur, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 1696. doi:
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    • Get Citation

      Daniel Sand, JeongGoo Lee, J Heur; Interleukin-1β enhances cell migration through AP-1 and NF-κB pathway dependent FGF2 expression in human corneal endothelial cells. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1696.

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Abstract

Purpose: To investigate IL-1β signaling in migration of human corneal endothelial cells (CECs).

Methods: Cell migration was measured using scratch-induced directional migration assay. Expression and/or activation of IRAK, PI 3-kinase, p38, IKK, IκB, NF-κB, and FGF-2 were analyzed by immunoblotting. AP-1 and NF-κB activities were measured by AP-1 and NF-κB ELISA assay kit, respectively. Binding of AP-1 and NF-κB to the promoter region of the FGF-2 gene was determined by chromatin immunoprecipitation.

Results: Stimulation of human CECs with IL-1β activated expression of FGF2 and resulted in enhanced cell migration. This, in turn, was abolished by treatment with either IL-1 receptor antagonist or SU-5402, a pan FGF inhibitor. PI 3-kinase or IRAK 1/4 antagonists demonstrated that IRAK 1/4 activates PI 3-kinase, which in turn phosphorylates p38 and IKK α/β, leading to FGF2 expression through activation of AP-1 and NF-κB in human CECs. Treatment of IL-1β stimulated human CECs, with either AP-1 or NF-κB antagonists, decreased FGF2 expression and resulted in reduced IL-1β enhanced cell migration. Co-treatment of IL-1β stimulated human CEC with both inhibitors completely blocked FGF2 expression and IL-1β enhanced cell migration. Chromatin immunoprecipitation assays demonstrated that AP-1 and NF-κB directly bind to the FGF2 promoter following IL-1β stimulation.

Conclusions: The results show that binding of IL-1β to its receptor in human CEC leads to parallel activation of AP-1 and NF-κB pathways, leading, in turn, to FGF2 expression and enhanced cell migration.

Keywords: 481 cornea: endothelium • 480 cornea: basic science  
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