title: Ellagic acid modulates the expression of oral innate immune mediators: potential role in mucosal protection.
abstract: BACKGROUND
  Ellagic acid (EA) found in various fruits such as pomegranates, blackberries, raspberries, strawberries, and walnuts has different pharmacological functions including antioxidant, antitumor, antiallergic, anti-inflammatory, antibacterial, and antiviral activities. It is not known, however, if EA could enhance mucosal innate immunity. Our goal was to determine the effects of EA on the expression of innate immune mediators produced by oral epithelial cells.
  
  
  METHODS
  Culture of primary human gingival epithelial cells (HGEs) was performed in duplicate, and after the primary HGEs had been treated with EA at a concentration ranging from 12.5 to 100 μM for 18 h the cells and supernatants were harvested. The expression of innate immune mediators including human β-defensin 2 (hBD2), secretory leukocyte protease inhibitor (SLPI), and various cytokines and chemokines was measured at both transcriptional and translational levels by using quantitative real-time PCR, ELISA, and Luminex assay.
  
  
  RESULTS
  In the presence of EA, the expression of hBD2-and SLPI mRNA was 3.7-folds and 2.6-folds greater than untreated controls, respectively, and consistent with their secreted protein levels. For cytokines and chemokines, increased expression of RANTES, IL-2, and IL-1β was found in response to EA. In contrast, EA decreased the expression of IL-6, IL-8, and TNF-α.
  
  
  CONCLUSIONS
  This study demonstrated that oral innate immunity is affected by EA found in fruits. Thus, it may play some roles in mucosal innate immunity. The potential of EA for modulating the innate immune mediators may lead to developing a new topical agent to treat and/or prevent immune-mediated oral diseases.
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand.
authors.forename: Aornrutai
authors.initials: A
authors.lastname: Promsong
authors.forename: Whasun Oh
authors.initials: WO
authors.lastname: Chung
authors.forename: Surada
authors.initials: S
authors.lastname: Satthakarn
authors.forename: Wipawee
authors.initials: W
authors.lastname: Nittayananta
mesh_terms: D018929:Cell Culture Techniques; D002478:Cells, Cultured; D054418:Chemokine CCL20 / Q000187:drug effects; D018946:Chemokine CCL5 / Q000187:drug effects; D054365:Chemokine CXCL5 / Q000187:drug effects; D018925:Chemokines / Q000187:drug effects; D016207:Cytokines / Q000187:drug effects; D004610:Ellagic Acid / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects; D005881:Gingiva / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects* / Q000276:immunology; D007155:Immunologic Factors / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000187:drug effects; D007376:Interleukin-2 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000187:drug effects; D010750:Phosphoproteins / Q000187:drug effects; D012269:Ribosomal Proteins / Q000187:drug effects; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects; D023083:beta-Defensins / Q000187:drug effects
chemical_list: C108355:CCL20 protein, human; C483024:CCL5 protein, human; C486263:CXCL5 protein, human; C508606:CXCL8 protein, human; D054418:Chemokine CCL20; D018946:Chemokine CCL5; D054365:Chemokine CXCL5; D018925:Chemokines; D016207:Cytokines; C106641:DEFB4A protein, human; C508594:IL2 protein, human; C508600:IL6 protein, human; D007155:Immunologic Factors; D053583:Interleukin-1beta; D007376:Interleukin-2; D015850:Interleukin-6; D016209:Interleukin-8; D010750:Phosphoproteins; D012269:Ribosomal Proteins; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D014409:Tumor Necrosis Factor-alpha; D023083:beta-Defensins; D004610:Ellagic Acid
keywords: cytokines; ellagic acid; hBD2; innate immunity; oral epithelial cells; secretory leukocyte protease inhibitor