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Interleukin-1β Enhances Cell Migration Through AP-1 and NF-κB Pathway-Dependent FGF2 Expression in Human Corneal Endothelial Cells

Interleukin-1β Enhances Cell Migration Through AP-1 and NF-κB Pathway-Dependent FGF2 Expression in Human Corneal Endothelial Cells

Jeong Goo Lee, Martin Heur

Biol Cell. 2013 Apr;105(4):175-89.

PMID: 23331079

Abstract:

Background information:
Interleukin (IL)-1β is a major pro-inflammatory cytokine that plays a crucial role in the regulation of inflammation and wound healing in the cornea. Elucidation of IL-1β signalling may help identify therapeutic targets for corneal wound healing; however, mechanisms such as cell migration, a component of IL-1β-induced wound healing response in human corneal endothelial cells (CEC), have not been well characterised.
Results:
Stimulation of human CEC with IL-1β activated expression of fibroblast growth factor 2 (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-fibroblast growth factor signalling inhibitor. Phosphatidyl inositol (PI) 3-kinase or IL receptor-associated kinase 1/4 antagonists demonstrated that IL receptor-associated kinase 1/4 activates PI 3-kinase, which in turn phosphorylates p38 and inhibitor κB kinase α/β, leading to FGF2 expression through activation of activator protein 1 (AP-1) and nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) in human CEC. Treatment of IL-1β-stimulated human CEC 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP215543923-A	SU-5402		215543-92-3	Price

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