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