title: Sucralfate prevents the delay of wound repair in intestinal epithelial cells by hydrogen peroxide through NF-kappaB pathway.
abstract: BACKGROUND
  Recent studies have shown that sucralfate (SF) has therapeutic effects on colonic inflammation in ulcerative colitis. The aim of this study was to clarify the function of SF for wound repair in intestinal epithelial cells (IEC).
  
  
  METHODS
  (1) Activation of signal proteins [ERK1/2 mitogen-activated protein kinase (MAPK), IkappaB-alpha] in IEC-6 cells after stimulation with 10(-4) M potassium sucrose octasulfate (SOS), which is the functional element of SF, was assessed by Western blot. (2) Induction of transforming growth factor (TGF)-beta1, TGF-alpha, EGF, and cyclooxygenase-2 (COX-2) mRNA after stimulation of IEC-6 cells with SOS was assessed by reverse transcriptase-polymerase chain reaction. (3) IEC-6 cells were wounded and cultured for 24 h with various concentrations of SOS in the absence or presence of 20 microM H(2)O(2). Epithelial migration or proliferation was assessed by counting migrating cells or bromodeoxyuridine (BrdU)-positive cells across the wound border.
  
  
  RESULTS
  (1) SOS activated IkappaB-alpha, but it did not activate ERK1/2 MAPK. (2) SOS enhanced the expression of COX-2 mRNA, but it did not change the mRNA expression of other growth factors. (3) SOS did not enhance wound repair in IEC-6 cells, but it decreased the number of dead cells (maximum, 74%) (P < 0.01) in a dose-dependent manner and prevented the diminishment of epithelial migration (maximum, 61%) (P < 0.01) and proliferation (maximum, 37%) (P < 0.05) induced by H(2)O(2). These functions of SOS were suppressed by the NF-kappaB and COX-2 inhibitors.
  
  
  CONCLUSIONS
  SOS prevented the delay of wound repair in IEC-6 cells induced by H(2)O(2), probably through induction of COX-2 and an anti-apoptotic mechanism. These effects of SOS might be given through the activation of the NF-kappaB pathway.
authors.affiliation: Department of Internal Medicine, Akita University School of Medicine, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Shindo
authors.forename: Masahiro
authors.initials: M
authors.lastname: Iizuka
authors.forename: Kenji
authors.initials: K
authors.lastname: Sasaki
authors.forename: Shiho
authors.initials: S
authors.lastname: Konno
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Itou
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Horie
authors.forename: Sumio
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000235:genetics; D015237:Dinoprost / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D008565:Membrane Proteins / Q000235:genetics; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D013392:Sucralfate / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000473:pathology / Q000503:physiopathology
chemical_list: D008565:Membrane Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D013392:Sucralfate; D015237:Dinoprost; D006861:Hydrogen Peroxide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human