title: Docosahexaenoic acid reduces linoleic acid induced monocyte chemoattractant protein-1 expression via PPARγ and nuclear factor-κB pathway in retinal pigment epithelial cells.
abstract: METHODS
  To investigate whether docosahexaenoic acid (DHA) could inhibit linoleic acid (LA) induced monocyte chemoattractant protein (MCP)-1 expression in human retinal pigment epithelial (RPE) cells.
  
  
  RESULTS
  ARPE-19 cells were pretreated with DHA and then exposed to LA. The expression of MCP-1 and PPARγ was examined using RT-PCR and Western blot analysis. LA at 10, 25, or 50 μM induced expression of MCP ARPE-19 cells in a dose-dependent manner (p < 0.05). DHA at 50 and 100 μM effectively inhibited LA-induced MCP-1 expression and production (p < 0.05) and NF-κB activation. In addition, the culture medium from LA-stimulated ARPE-19 cells could induce tube formation in choroidal endothelial cells (RF6A), whereas 100 μM DHA inhibited tube formation. DHA at 100 μM increased the expression and activity of PPARγ (p < 0.05). Pretreatment with PPARγ inhibitor (GW9662) abolished the inhibitory effect of DHA (100 μM) on LA-induced IκB degradation, p65 translocation, and MCP-1 expression in ARPE-19 cells (p < 0.05), as well as tube formation in RF6A.
  
  
  CONCLUSIONS
  DHA reduced LA-induced MCP-1 expression via a PPARγ- and NF-κB-dependent pathway in ARPE-19 cells. These results suggest the molecular mechanisms underlying the beneficial effects of increased consumption of DHA and reduced consumption of LA on age-related macular degeneration.
authors.affiliation: Department of Ophthalmology, Taipei City Hospital, Zhongxiao Branch, Taipei, Taiwan; Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: I-Mo
authors.initials: IM
authors.lastname: Fang
authors.forename: Chang-Hao
authors.initials: CH
authors.lastname: Yang
authors.forename: Chung-May
authors.initials: CM
authors.lastname: Yang
mesh_terms: D000813:Anilides / Q000494:pharmacology; D016718:Arachidonic Acid / Q000009:adverse effects / Q000037:antagonists & inhibitors; D002460:Cell Line; D018932:Chemokine CCL2 / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D002829:Choroid / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D020256:Choroidal Neovascularization / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D017077:Culture Media, Conditioned / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000378:metabolism* / Q000627:therapeutic use; D015118:Eicosapentaenoic Acid / Q000378:metabolism / Q000627:therapeutic use; D005230:Fatty Acids, Nonesterified / Q000009:adverse effects / Q000037:antagonists & inhibitors; D006801:Humans; D019787:Linoleic Acid / Q000009:adverse effects / Q000037:antagonists & inhibitors; D008268:Macular Degeneration / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009994:Osmolar Concentration; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D017077:Culture Media, Conditioned; D005230:Fatty Acids, Nonesterified; D016328:NF-kappa B; D047495:PPAR gamma; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D019787:Linoleic Acid; D015118:Eicosapentaenoic Acid
keywords: Docosahexaenoic acid; Linoleic acid; Monocyte chemoattractant protein-1; Neovascularization; Peroxisome proliferator-activated receptors