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Common and Distinct Pathways for Cellular Activities in FGF-2 Signaling Induced by IL-1β in Corneal Endothelial Cells

¹From the Doheny Eye Institute and the ²Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California.

PURPOSE. To determine the mechanism by which IL-1β induces FGF-2 and to elucidate the signaling pathways of IL-1β–induced FGF-2 in corneal endothelial cells (CECs).

METHODS. Expression and/or activation of FGF-2, p38, ERK1/2, and Akt was analyzed by immunoblot analysis. Cell proliferation was measured by MTT assay. Pharmacologic inhibitors were used to block PI 3-kinase, p38, or ERK1/2.

RESULTS. Brief stimulation of CECs with IL-1β activated PI 3-kinase and p38 in a biphasic fashion. The first wave of activation, triggered by IL-1β, involves the inductive activity of IL-1β on FGF-2 production; the second wave of activation, triggered by the induced FGF-2, involves the promotion of cellular activities. In both pathways, p38 acts downstream to PI 3-kinase. The inductive activity of IL-1β on FGF-2 is further evidenced by the conditioned medium, which contains a large amount of FGF-2. Stimulation of CECs with IL-1β also activated ERK1/2 in a delayed fashion. The IL-1β–induced FGF-2 exerted cellular activities using distinct pathways: the second wave of activation of PI 3-kinase and p38 was involved in cell migration, whereas cell proliferation was simultaneously stimulated by ERK1/2 and the second wave of PI 3-kinase. Likewise, the conditioned medium demonstrated cellular activities and pathways identical with those observed in cells treated with IL-1β.

CONCLUSIONS. These data suggest that CECs produce FGF-2 by IL-1β stimulation through PI 3-kinase and p38. The IL-1β–induced FGF-2 facilitates cell migration via PI 3-kinase and p38, whereas it stimulates cell proliferation using PI 3-kinase and ERK1/2 in parallel pathways.

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				J.-S. Song, J. G. Lee, and E. P. Kay Induction of FGF-2 Synthesis by IL-1{beta} in Aqueous Humor through P13-Kinase and p38 in Rabbit Corneal Endothelium Invest. Ophthalmol. Vis. Sci., February 1, 2010; 51(2): 822 - 829. [Abstract] [Full Text] [PDF]