title: Lycopene inhibits ICAM-1 expression and NF-κB activation by Nrf2-regulated cell redox state in human retinal pigment epithelial cells.
abstract: OBJECTIVE
  Age-related macular degeneration (AMD) is one of the most common diseases leading to blindness in elderly people. The progression of AMD may be prevented through anti-inflammation and antioxidation in retinal pigment epithelium (RPE) cells. Lycopene, a carotenoid, has been shown to possess both antioxidative and anti-inflammatory properties. This research was conducted to detail the mechanisms of these effects of lycopene-treated RPE cells.
  
  
  METHODS
  We exposed ARPE-19 cells to TNFα after pretreatment with lycopene, and measured monocyte adhesion, ICAM-1 expression, NF-κB nuclear translocation, and transcriptional activity. Cell viability was assayed with Alamar Blue. The cell redox state was tested by glutathione (GSH) and reactive oxygen species (ROS) levels. The importance of the Nrf2 pathway was tested in nuclear translocation, promoter reporter assay, and siRNA.
  
  
  RESULTS
  Lycopene could reduce TNF-α-induced monocyte adhesion and H2O2- induced cell damage in RPE cells. Furthermore, lycopene inhibits ICAM-1 expression and abolishes NF-κB activation for up to 12h in TNFα-treated RPE cells. Lycopene upregulates Nrf2 levels in nuclear extracts and increases the transactivity of antioxidant response elements. The use of Nrf2 siRNA blocks the inhibitory effect of lycopene in TNF-α-induced ICAM-1 expression and NF-κB activation. Glutamate-cysteine ligase (GCL) is the rate-limiting enzyme in the de novo synthesis of GSH. We found that lycopene increases intracellular GSH levels and GCL expression. Following lycopene treatment, TNF-α-induced ROS production was abolished.
  
  
  CONCLUSIONS
  The Nrf2-regulated antioxidant property plays a pivotal role in the anti-inflammatory mechanism underlying the inhibition of NF-κB activation in lycopene-treated ARPE-19 cells.
authors.affiliation: Department of Ophthalmology, Chiayi Christian Hospital, Chiayi, Taiwan, ROC; Department of Microbiology, Immunology and Biopharmaceuticals, National Chiayi University, Chiayi, Taiwan, ROC.
authors.forename: Po-Min
authors.initials: PM
authors.lastname: Yang
authors.affiliation: Department of Microbiology, Immunology and Biopharmaceuticals, National Chiayi University, Chiayi, Taiwan, ROC.
authors.forename: Zhi-Zhen
authors.initials: ZZ
authors.lastname: Wu
authors.affiliation: Department of Microbiology, Immunology and Biopharmaceuticals, National Chiayi University, Chiayi, Taiwan, ROC.
authors.forename: Yu-Qi
authors.initials: YQ
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, Immunology and Biopharmaceuticals, National Chiayi University, Chiayi, Taiwan, ROC. Electronic address: bswung@mail.ncyu.edu.tw.
authors.forename: Being-Sun
authors.initials: BS
authors.lastname: Wung
mesh_terms: D002338:Carotenoids / Q000494:pharmacology*; D002478:Cells, Cultured; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D000077276:Lycopene; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010084:Oxidation-Reduction; D034741:RNA, Small Interfering / Q000235:genetics; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; D034741:RNA, Small Interfering; D018799:Intercellular Adhesion Molecule-1; D002338:Carotenoids; D000077276:Lycopene
keywords: Intercellular adhesion molecule-1; Lycopene; Nrf2; Nuclear factor-κB; Retinal pigment epithelial cell