title: Interleukin-1β enhances cell migration through AP-1 and NF-κB pathway-dependent FGF2 expression in human corneal endothelial cells.
abstract: BACKGROUND
  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.
authors: Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA.
authors: Jeong Goo
authors: JG
authors: Lee
authors: Martin
authors: M
authors: Heur
mesh_terms: D002460:Cell Line; D002465:Cell Movement; D003315:Cornea / Q000166:cytology* / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D053583:Interleukin-1beta; D016328:NF-kappa B; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D016222:Fibroblast Growth Factor 2