Korean Journal of Pediatrics 2010;53(4):525-531.
Published online April 15, 2010.
Apoptosis and upregulation of TNF-α and TRAIL receptor 1 (DR4) in the pathogenesis of food protein-induced enterocolitis syndrome
Jin-Bok Hwang1, Sang Pyo Kim2, Yu Na Kang2, Seong-Ryong Lee3, Seong-Il Suh3, Taeg Kyu Kwon3
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
우유 단백질 유발성 장염 증후군의 병리 기전으로 세포 자멸사와 TNF-α, TRAIL receptor 1 (DR4)의 발현 증가
황진복1, 김상표2, 강유나2, 이성룡3, 서성일3, 권택규3
1계명대학교 의과대학 소아과학교실
2계명대학교 의과대학 병리학교실
3계명대학교 의과대학 의과학연구소
Correspondence: 
Jin-Bok Hwang, Email: pedgi@kmu.ac.kr
Abstract
Purpose
: Expression levels of tumor necrosis factor (TNF)-α expression on the mucosa of the small intestine is increased in patients with villous atrophy in food protein-induced enterocolitis syndrome (FPIES). TNF-α 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-α, 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-α (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-α expression and DR4 pathway may have an important role in apoptosis.
Key Words: Food protein-induced enterocolitis syndrome, Etiology, Apoptosis, Tumor necrosis factor-alpha, TNF-related apoptosis-including ligand receptor 1


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