期刊
JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION
卷 54, 期 5, 页码 630-638出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MPG.0b013e31823e7c29
关键词
immature intestinal epithelium; modulation of immune response; TGF-beta
资金
- Academy of Finland
- Finnish Society for Pediatric Research
- Foundation for Medical Research in Finland
- Helsingin Sanomat Foundation
- [NIH R01-HD12437]
- [R01-DK70260]
- [P01-DK33506]
- [P30-DK40561]
- [NIH R01-HD059126]
Objectives: Breast milk transforming growth factor (TGF)-beta 2 is associated with healthy immune maturation and reduced risk of immune-mediated disease in infants. We sought to investigate whether conditioning with TGF-beta 2 may result in a more mature immune responder phenotype in immature human intestinal epithelial cells (IECs). Methods: Primary human fetal IECs (hFIECs) and the human fetal small intestinal epithelial cell line (H4 cells) were conditioned with breast milk levels of TGF-beta 2, and an inflammatory response was subsequently induced. Inflammatory cytokine secretion and mRNA expression were measured by enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction, respectively. Alterations in activation of inflammatory signaling pathways were detected from IECs by immunoblotting and immunofluorescence. The effects of TGF-beta 2 conditioning on gene expression patterns in hFIECs were assessed by cDNA microarray analysis and quantitative PCR. Results: Conditioning with TGF-beta 2 significantly attenuated subsequent interleukin (IL)-1 beta-, TNF-alpha-, and poly I: C-induced IL-8 and IL-6 responses in immature human IECs. Conditioning with TGF-beta 2 inhibited IL-1 beta-induced I kappa B-alpha degradation and NF-kappa B p65 nuclear translocation, which may partially result from TGF-beta 2-induced changes in the expression of genes in the NF-kappa B signaling pathway detected by cDNA microarray and qPCR. Conclusions: Conditioning with TGF-beta 2 attenuates the subsequent inflammatory cytokine response in immature human IECs by inhibiting signaling in the NF-kappa B pathway. The immunomodulatory potential of breast milk may in part be mediated by TGF-beta 2, which may provide a novel means of supporting intestinal immune maturation in neonates.
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