title: IL-1 stimulates ceramide accumulation without inducing apoptosis in intestinal epithelial cells.
abstract: BACKGROUND
  In inflammatory bowel disease (IBD), cytokine levels (such as interleukin-1 (IL-1)) are elevated. We have shown previously that IL-1 activates phospholipid signaling pathways in intestinal epithelial cells (EEC), leading to increased ceramide levels.
  
  
  OBJECTIVE
  To determine whether ceramide induces apoptosis in IEC.
  
  
  METHODS
  Apoptosis was evaluated by annexin-V binding or Hoechst nuclear staining. Levels of bcl-2, bcl-x, bax, p53 and p21 were determined by Western blotting, and celi cycle analysis was determined by flow cytometry.
  
  
  RESULTS
  IL-1 increased ceramide accumulation in a time-dependent and concentration-dependent manner with a peak response at 4 h, with [IL-1] = 30 ng/ml. Neither IL-1 nor ceramide induced apoptosis in EEC, but they increased bcl-2 levels and decreased bax and p21 levels without affecting bcl-x and p53 levels. They also caused a slight but significant increase in the G2/M phase. These data suggest a role for ceramide in IBD and suggest a possible mechanism for the enhanced tumorigenic activity in IBD patients.
authors.affiliation: Department of Physiology, Faculty of Medicine, American University of Beirut, Lebanon. fh01@aub.edu.lb
authors.forename: Fadia R
authors.initials: FR
authors.lastname: Homaidan
authors.forename: Marwan E
authors.initials: ME
authors.lastname: El-Sabban
authors.forename: Iman
authors.initials: I
authors.lastname: Chakroun
authors.forename: Mirvat
authors.initials: M
authors.lastname: El-Sibai
authors.forename: Ghassan S
authors.initials: GS
authors.lastname: Dbaibo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002518:Ceramides / Q000096:biosynthesis* / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
chemical_list: D002518:Ceramides; D007375:Interleukin-1; D016159:Tumor Suppressor Protein p53