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Korean J Pediatr 2010 April;53(4) :525-531.
Apoptosis and upregulation of TNF- and TRAIL receptor 1 (DR4) in the pathogenesis of food protein-induced enterocolitis syndrome
Jin-Bok Hwang (Hwang JB)1, Sang Pyo Kim (Kim SP)2, Yu Na Kang (Kang YN)2, Seong-Ryong Lee (Lee SR)3, Seong-Il Suh (Suh SI)3, Taeg Kyu Kwon (Kwon TK)3
1Departments of Pathology, Keimyung University School of Medicine, Daegu, Korea
2Departments of Pathology, Keimyung University School of Medicine, Daegu, Korea
3Institute for Medical Science, Keimyung University School of Medicine, Daegu, Korea
Corresponding Author: Jin-Bok Hwang ,Email:
Copyright © 2010 by The Korean Pediatric Society
Purpose : Expression levels of tumor necrosis factor (TNF)- expression on the mucosa of the small intestine is increased in patients with villous atrophy in food protein-induced enterocolitis syndrome (FPIES). TNF- has been reported to induce apoptotic cell death in the epithelial cells. We studied the TNF family and TNF-receptor family apoptosis on the duodenal mucosa to investigate their roles in the pathogenesis of FPIES. Methods : Fifteen infants diagnosed as having FPIES using standard oral challenge test and 5 controls were included. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining was performed to identify the apoptotic cell death bodies. Immunohistochemical staining of TNF-, Fas ligand (FasL) for TNF family and TNF-related apoptosis-including ligand (TRAIL) receptor 1 (DR4), TRAIL receptor 2 (DR5), and Fas for TNF-receptor family were performed to determine the apoptotic mechanisms. Results : TUNEL+ was significantly more highly expressed in the duodenal mucosa of FPIES patients than in controls (P = 0.043). TNF- (P =0.0001) and DR4 (P =0.003) were significantly more highly expressed in FPIES patients than in controls. Expression levels of FasL, Fas, and DR5 were low in both groups and were not significantly different between the 2 groups. Conclusion : These results suggest that FPIES pathogenesis is induced by apoptosis, and that TNF- expression and DR4 pathway may have an important role in apoptosis.
Keywords: Food protein-induced enterocolitis syndrome | Etiology | Apoptosis | Tumor necrosis factor-alpha | TNF-related apoptosis-including ligand receptor 1
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