Heparin-binding EGF-like growth factor decreases apoptosis in intestinal epithelial cells in vitro

Background/Purpose: The production of heparin-binding EGF-like growth factor (HB-EGF) is upregulated during organ injury and has a cytoprotective effect during hypoxic stress in intestinal epithelial cells in vitro and intestinal ischemia/reperfusion injuries in vivo. The purpose of this study was to determine if HB-EGF-related cytoprotection is manifested through alterations in apoptosis. Methods: Human intestinal epithelial cell monolayers (DLD-1 and Caco-2) were stimulated with interleukin (IL)-1 (20 ng/mL), tumor necrosis factor (TNF)-alpha (40 ng/mL), and interferon (IFN)-gamma (10 ng/mL) with or without HB-EGF (1, 10 or 100 ng/mL) and analyzed for rates of apoptosis utilizing a Cell Death Detection ELISA and flow cytometry. Results: ELISA results showed a 3-fold increase in the level of apoptosis during stimulation with cytokines compared with nonstimulated cells (P <.05). Relative levels of cytokine-induced apoptosis were reduced after 12 hours of HB-EGF exposure (P <.05) in a dose-dependent fashion. Results of flow cytometric analysis also showed a reduction in apoptosis at 6 hours when cell monolayers were stimulated with cytokines in conjunction with HB-EGF compared with cytokines alone (P <.05). Conclusions: HB-EGF downregulated apoptosis in intestinal epithelial cells exposed to proinflammatory cytokines in vitro. The results of this study suggest that alterations in apoptosis may represent a possible mechanism by which this growth factor exerts its cytoprotective effect at the mucosal level during the proinflammatory state. J Pediatr Surg 36:1130-1135. Copyright (C) 2001 by W.B. Saunders Company.