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Eur J Pediatr Surg 2016; 26(03): 260-266
DOI: 10.1055/s-0035-1551563
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Interleukin-23 Increases Intestinal Epithelial Cell Permeability In Vitro

Nathan P. Heinzerling
1   Division of Pediatric Surgery, Medical College of Wisconsin, Children's Hospital of Wisconsin, Milwaukee, Wisconsin, United States
,
Deborah Donohoe
2   Division of Critical Care, Medical College of Wisconsin, Children's Hospital of Wisconsin, Milwaukee, Wisconsin, United States
,
Katherine Fredrich
1   Division of Pediatric Surgery, Medical College of Wisconsin, Children's Hospital of Wisconsin, Milwaukee, Wisconsin, United States
,
David M. Gourlay
1   Division of Pediatric Surgery, Medical College of Wisconsin, Children's Hospital of Wisconsin, Milwaukee, Wisconsin, United States
,
Jennifer L. Liedel
2   Division of Critical Care, Medical College of Wisconsin, Children's Hospital of Wisconsin, Milwaukee, Wisconsin, United States
3   Division of Neonatology, Medical College of Wisconsin, Children's Hospital of Wisconsin, Milwaukee, Wisconsin, United States
› Author Affiliations
Further Information

Publication History

15 May 2014

15 February 2015

Publication Date:
22 May 2015 (online)

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Abstract

Background Breast milk has a heterogeneous composition that differs between mothers and changes throughout the first weeks after birth. The proinflammatory cytokine IL-23 has a highly variable expression in human breast milk. We hypothesize that IL-23 found in human breast milk is biologically active and promotes epithelial barrier dysfunction.

Methods The immature rat small intestinal epithelial cell line, IEC-18, was grown on cell inserts or standard cell culture plates. Confluent cultures were exposed to human breast milk with high or low levels of IL-23 and barrier function was measured using a flux of fluorescein isothiocyanate–dextran (FD-70). In addition, protein and mRNA expression of occludin and ZO-1 were measured and immunofluorescence used to stain occludin and ZO-1.

Results Exposure to breast milk with high levels of IL-23 caused an increase flux of FD-70 compared with both controls and breast milk with low levels of IL-23. The protein expression of ZO-1 but not occludin was decreased by exposure to high levels of IL-23. These results correlate with immunofluorescent staining of ZO-1 and occludin which show decreased staining of occludin in both the groups exposed to breast milk with high and low IL-23. Conversely, cells exposed to high IL-23 breast milk had little peripheral staining of ZO-1 compared with controls and low IL-23 breast milk.

Conclusion IL-23 in human breast milk is biologically active and negatively affects the barrier function of intestinal epithelial cells through the degradation of tight junction proteins.

Keywords

IL-23 - gut barrier - tight junctions - necrotizing enterocolitis

Note

The Children's Research Institute supported this research.


 

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