Interleukin-23 Increases Intestinal Epithelial Cell Permeability In Vitro.

Area of Science:

• Immunology
• Gastroenterology
• Neonatal Research

Background:

• Human breast milk composition varies significantly between mothers and over time.
• The proinflammatory cytokine, Interleukin-23 (IL-23), exhibits high variability in breast milk.
• IL-23's biological activity and role in promoting epithelial barrier dysfunction in breast milk are not fully understood.

Purpose of the Study:

• To investigate the biological activity of IL-23 present in human breast milk.
• To determine if breast milk IL-23 negatively impacts intestinal epithelial barrier function.
• To elucidate the molecular mechanisms by which breast milk IL-23 affects tight junction proteins.

Main Methods:

• Utilized the immature rat intestinal epithelial cell line (IEC-18) cultured on cell inserts.
• Exposed IEC-18 cells to human breast milk with varying levels of IL-23.
• Assessed barrier function via fluorescein isothiocyanate-dextran (FD-70) flux and measured occludin and ZO-1 protein/mRNA expression and localization via immunofluorescence.

Main Results:

• Exposure to high IL-23 breast milk significantly increased FD-70 flux, indicating impaired barrier function.
• Protein expression of ZO-1 was decreased, while occludin expression was not significantly altered by high IL-23.
• Immunofluorescence revealed reduced occludin staining and peripheral ZO-1 staining in cells exposed to high IL-23 breast milk.

Conclusions:

• Interleukin-23 (IL-23) in human breast milk is biologically active.
• Breast milk IL-23 negatively affects intestinal epithelial barrier function.
• IL-23 contributes to barrier dysfunction through the degradation of tight junction proteins like ZO-1 and occludin.