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 (IEC), leading to increased ceramide levels.
Aim: To determine whether ceramide induces apoptosis in IEC.
Methods: Apoptosis was evaluated by annexin-Vbinding or Hoechst nuclear staining. Levels of bcl-2, bcl-x, bax, p53 and p21 were determined by Western blotting, and cell 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 IEC, 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.
Citation:
Homaidan, F. R., El-Sabban, M. E., Chakroun, I., El-Sibai, M., & Dbaibo, G. S. (2002). IL-1 stimulates ceramide accumulation without inducing apoptosis in intestinal epithelial cells. Mediators of inflammation, 11(1), 39-45.
