May 2008
Volume 49, Issue 13
ARVO Annual Meeting Abstract  |   May 2008
Upregulation of IL-1β-Induced FGF-2 Expression and Cell Migration by Activated p38 Through the Action of PI-3 Kinase in Corneal Endothelial Cells
Author Affiliations & Notes
  • J. Lee
    Doheny Eye Institute, Los Angeles, California
  • E. P. Kay
    Doheny Eye Institute, Los Angeles, California
    Ophthalmology, Keck School of Medicine of University of Southern California, Los Angeles, California
  • Footnotes
    Commercial Relationships  J. Lee, None; E.P. Kay, None.
  • Footnotes
    Support  NIH/NEI 06431and 03040, and Research to Prevent Blindness, New York, NY.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 3960. doi:
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      J. Lee, E. P. Kay; Upregulation of IL-1β-Induced FGF-2 Expression and Cell Migration by Activated p38 Through the Action of PI-3 Kinase in Corneal Endothelial Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3960. doi:

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

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Purpose: : Our previous work demonstrated that IL-1β, a major proinflammatory cytokine, plays a role in endothelial to mesenchymal transformation of corneal endothelial cells (CECs) through its inductive potential on FGF-2 via the action of PI 3-kinase. We further investigated the downstream signaling pathway of IL-1β for FGF-2 induction and its effect on cell migration.

Methods: : Expression of IRAK, TRAF-6, Akt, p38, ERK1/2, and FGF-2 was analyzed by immunoblotting. The phosphorylation of Akt, p38, and ERK1/2 was also detected by immunoblotting. SB203580 and LY294002 were used to inhibit p38 and PI 3-kinase, respectively. Scratch-induced directional migration assay was employed to measure migratory rates.

Results: : Among the downstream kinases, Akt, p38 and ERK1/2 were constitutively expressed, while expression of IRAK and TRAF-6 was temporally induced by IL-1β treatment. We next examined whether activation of p38, ERK1/2 and Akt was induced by IL-1β. A marked phosphorylation of p38 and Akt at Ser473 site was observed 60 min after IL-1β stimulation, but phosphorylation of ERK and Akt at Thr308 site was not detected. To determine the hierarchy of the two signal proteins, p38 and PI 3-kinase, we examined the effect of PI 3-kinase inhibition on p38 activation and vice versa. LY294002 markedly reduced phosphorylation of p38, whereas the level of the active Akt was not affected by inhibition of p38, suggesting that PI 3-kinase lies upstream of p38 in the IL-1β signaling pathway. The inhibition of p38 activation also prevents the induction of FGF-2 caused by IL-1β. We further investigated whether IL-1β induced cell migration. Stimulation with IL-1β alone resulted in a 65% recovery of the wound area with a fast migratory speed (0.8 µm/min), while CECs simultaneously treated with IL-1β and SB203580 achieved a 20% recovery of the wound area, suggesting the involvement of p38 and PI 3-kinase in endothelial migration by IL-1β treatment.

Conclusions: : These findings suggest that induction of FGF-2 by IL-1β was mediated by phosphos-p38 and phosphos-AktSer473 through PI 3-kinase and that endothelial migration was also induced by IL-1β signaling mediated by activated p38 via PI 3-kinase.

Keywords: cornea: endothelium • signal transduction 

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