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

Mediators of Inflammation
Fadia R HomaidanG S Dbaibo

Abstract

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. To determine whether ceramide induces apoptosis in IEC. 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. 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.

Citations

May 29, 2008·World Journal of Gastroenterology : WJG·Riina-A KekkonenRiitta Korpela
Dec 23, 2009·World Journal of Gastroenterology : WJG·Kajsa KajanderRiitta Korpela
Feb 18, 2016·Mediators of Inflammation·Loubna Abdel HadiLaura Riboni
Jul 16, 2016·Scientific Reports·Sara Al-GhadbanMarwan E El-Sabban
Jan 31, 2018·Scientific Reports·Fabian P S YuJeffrey A Medin
Oct 20, 2020·Frontiers in Immunology·Bhagirath ChaurasiaScott A Summers

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