title: Involvement of intracellular calcium mobilization in IL-8 activation in human retinal pigment epithelial cells.
abstract: OBJECTIVE
  Calcium signaling is an important intracellular pathway. Increased intracellular calcium is associated with cytokine regulation and inflammatory signals secretion. The purpose of this study is to understand the molecular mechanisms by which calcium signaling controls IL-8 activation in human RPE cells.
  
  
  METHODS
  Fluorescence-based calcium imaging and different mutants of IL-8 plasmids were used in this study. The IL-8 promoter activation, gene expression, and secretion were detected by using luciferase reporter assay, quantitative real-time PCR (Q-PCR), and ELISA, respectively. In addition, pharmacological inhibitors and small interfering RNA (siRNA) were applied to clarify the mechanisms of IL-8 activation.
  
  
  RESULTS
  Our study reported that intracellular calcium mobilization activated IL-8 gene expression and secretion. Application of pharmacological inhibitor BAY 11-7082, siRNA, and plasmids of the nuclear factor κ light chain enhancer of activated B cells (NF-κB) binding site, we identified that NF-κB is the main transcription factor involved in intracellular calcium mobilization-mediated IL-8 activation in human RPE cells.
  
  
  CONCLUSIONS
  Collectively, our findings highlight the important role of intracellular calcium mobilization in the activation of IL-8. These findings may be helpful for the clinical applications in the age-related macular degeneration (AMD) prevention and treatment.
authors.affiliation: Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: I-Hui
authors.initials: IH
authors.lastname: Yang
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan Department of Medical Genetics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Jhen-Hong
authors.initials: JH
authors.lastname: Wong
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Che-Mai
authors.initials: CM
authors.lastname: Chang
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ben-Kuen
authors.initials: BK
authors.lastname: Chen
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan Department of Medical Genetics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yao-Ting
authors.initials: YT
authors.lastname: Tsai
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Wei-Chiao
authors.initials: WC
authors.lastname: Chen
authors.affiliation: Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Eric Terry
authors.initials: ET
authors.lastname: Wang
authors.affiliation: Department of Medical Genetics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Wen-Li
authors.initials: WL
authors.lastname: Hsu
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan Department of Pharmacy, Taipei Medical University Wan Fang Hospital, Taipei, Taiwan Comprehensive Cancer Center, Taipei Medical University, Taipei, Taiwan.
authors.forename: Wei-Chiao
authors.initials: WC
authors.lastname: Chang
mesh_terms: D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics*; D008268:Macular Degeneration / Q000378:metabolism* / Q000473:pathology; D012313:RNA / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D055213:Retinal Pigment Epithelium / Q000378:metabolism* / Q000473:pathology
chemical_list: D016209:Interleukin-8; D012313:RNA; D002118:Calcium
keywords: IL-8; calcium; retinal pigment epithelium