title: Curcumin ameliorates hydrogen peroxide-induced epithelial barrier disruption by upregulating heme oxygenase-1 expression in human intestinal epithelial cells.
abstract: BACKGROUND
  Disruption of epithelial tight junctions (TJ) followed by loss of barrier function is of crucial importance in the pathogenesis of a variety of gastrointestinal disorders. Heme oxygenase-1 (HO-1), which can be induced by curcumin (Cur), provides protection against various forms of oxidative stress.
  
  
  OBJECTIVE
  The protective effect of Cur on oxidative stress-induced intestinal barrier disruption in human intestinal epithelial cells was elucidated in this study.
  
  
  METHODS
  H(2)O(2)-induced Caco-2 enterocytic monolayers were incubated in the presence or absence of Cur and/or zinc protoporphyrin (ZnPP). The trans-epithelial electrical resistance (TEER) and the flux of sodium fluorescein in the filter-grown Caco-2 cell monolayers were measured. The expression and localization of the TJ protein occludin and zonula occluden-1 (ZO-1) were evaluated by western blot and immunofluorescence microscopy. The mRNA and protein levels of HO-1 were analyzed by real-time PCR and western blot.
  
  
  RESULTS
  Cur attenuated H(2)O(2)-induced disruption of paracellular permeability (TEER 52.02 ± 10.15% vs 22.71 ± 3.11%; sodium fluorescein flux 12.41 ± 2.19% vs 32.00 ± 4.97%, P < 0.05) and induced HO-1 mRNA (6.64 ± 0.48 vs 3.22 ± 0.28, P < 0.05) and protein (291.00 ± 9.17% vs 99.00 ± 10.00%, P < 0.05) expression in Caco-2 cells. After administration of H(2)O(2), occludin and ZO-1 proteins were restored by Cur (occludin 175.67 ± 29.50% vs 53.67 ± 24.19%, P < 0.05; ZO-1 139.67 ± 33.71% vs 36.00 ± 15.88%, P < 0.05) and this effect was blocked by HO-1 inhibitor, ZnPP (occludin 54.67 ± 10.02% vs 168.33 ± 36.47%, P < 0.05; ZO-1 50.00 ± 15.13% vs 117.67 ± 38.81%, P < 0.05).
  
  
  CONCLUSIONS
  Cur protects human intestinal epithelial cells against H(2)O(2)-induced disruption of TJ and barrier dysfunction via the HO-1 pathway.
authors.affiliation: Department of Gastroenterology, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.forename: Gai
authors.initials: G
authors.lastname: Wang
authors.forename: JingXia
authors.initials: J
authors.lastname: Hao
authors.forename: JunJi
authors.initials: J
authors.lastname: Ma
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: XiaoYu
authors.initials: X
authors.lastname: Jiang
authors.forename: HuiQing
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D018938:Caco-2 Cells; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D019108:Tight Junctions / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D006861:Hydrogen Peroxide; D051547:Heme Oxygenase-1; D003474:Curcumin