Common and distinct pathways for cellular activities in FGF-2 signaling induced by IL-1beta in corneal endothelial cells.

Abstract:

PURPOSE:To determine the mechanism by which IL-1beta induces FGF-2 and to elucidate the signaling pathways of IL-1beta-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-1beta activated PI 3-kinase and p38 in a biphasic fashion. The first wave of activation, triggered by IL-1beta, involves the inductive activity of IL-1beta 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-1beta on FGF-2 is further evidenced by the conditioned medium, which contains a large amount of FGF-2. Stimulation of CECs with IL-1beta also activated ERK1/2 in a delayed fashion. The IL-1beta-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-1beta. CONCLUSIONS:These data suggest that CECs produce FGF-2 by IL-1beta stimulation through PI 3-kinase and p38. The IL-1beta-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.

authors

Lee JG,Kay EP

doi

10.1167/iovs.08-3135

subject

Has Abstract

pub_date

2009-05-01 00:00:00

pages

2067-76

issue

5

eissn

0146-0404

issn

1552-5783

pii

iovs.08-3135

journal_volume

50

pub_type

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