Korean J Pediatr.  2010 Apr;53(4):525-531. 10.3345/kjp.2010.53.4.525.

Apoptosis and upregulation of TNF-alpha and TRAIL receptor 1 (DR4) in the pathogenesis of food protein-induced enterocolitis syndrome

• Hwang JB
• Kim SP
• Kang YN
• Lee SR
• Suh SI
• Kwon TK

• KMID: 2073578
• DOI: http://doi.org/10.3345/kjp.2010.53.4.525

Abstract

PURPOSE
Expression levels of tumor necrosis factor (TNF)-alpha expression on the mucosa of the small intestine is increased in patients with villous atrophy in food protein-induced enterocolitis syndrome (FPIES). TNF-alpha 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-alpha, 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-alpha (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-alpha expression and DR4 pathway may have an important role in apoptosis.

Keyword

Food protein-induced enterocolitis syndrome; Etiology; Apoptosis; Tumor necrosis factor-alpha; TNF-related apoptosis-including ligand receptor 1

MeSH Terms

Apoptosis
Atrophy
Cell Death
Enterocolitis
Epithelial Cells
Fas Ligand Protein
Humans
Infant
Intestine, Small
Mucous Membrane
Receptors, TNF-Related Apoptosis-Inducing Ligand
Tumor Necrosis Factor-alpha
Up-Regulation
Fas Ligand Protein
Receptors, TNF-Related Apoptosis-Inducing Ligand
Tumor Necrosis Factor-alpha