IL-1 stimulates ceramide accumulation without inducing apoptosis in intestinal epithelial cells

Fadia R. Homaidan ； Marwan E. El-Sabban ； Iman Chakroun ； Mirvat El-Sibai ； Ghassan S. Dbaibo

《Mediators of Inflammation》 2002卷 (2002/12) Pp. 39-45

https://doi.org/10.1080/09629350120117284

摘要

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 pathway s in intestinal epithelial cells (IEC), leading to increased ceramide levels. Aim: To determine whether ceramide induces apopto - sis 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 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 apopto sis 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.

關鍵字

Epithelial cells ； IL-1 ； bcl-2 ； bcl-x ； bax ； IBD ； Inflammation