Skip Navigation LinksHome > May 2012 - Volume 54 - Issue 5 > TGF-β2 Induces Maturation of Immature Human Intestinal Epith...
Journal of Pediatric Gastroenterology & Nutrition:
doi: 10.1097/MPG.0b013e31823e7c29
Original Articles: Gastroenterology

TGF-β2 Induces Maturation of Immature Human Intestinal Epithelial Cells and Inhibits Inflammatory Cytokine Responses Induced Via the NF-κB Pathway

Rautava, Samuli; Lu, Lei; Nanthakumar, N. Nanda; Dubert-Ferrandon, Alix; Walker, W. Allan

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Objectives: Breast milk transforming growth factor (TGF)-β2 is associated with healthy immune maturation and reduced risk of immune-mediated disease in infants. We sought to investigate whether conditioning with TGF-β2 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-β2, 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-β2 conditioning on gene expression patterns in hFIECs were assessed by cDNA microarray analysis and quantitative PCR.

Results: Conditioning with TGF-β2 significantly attenuated subsequent interleukin (IL)-1β-, TNF-α-, and poly I:C-induced IL-8 and IL-6 responses in immature human IECs. Conditioning with TGF-β2 inhibited IL-1β-induced IκB-α degradation and NF-κB p65 nuclear translocation, which may partially result from TGF-β2-induced changes in the expression of genes in the NF-κB signaling pathway detected by cDNA microarray and qPCR.

Conclusions: Conditioning with TGF-β2 attenuates the subsequent inflammatory cytokine response in immature human IECs by inhibiting signaling in the NF-κB pathway. The immunomodulatory potential of breast milk may in part be mediated by TGF-β2, which may provide a novel means of supporting intestinal immune maturation in neonates.

Copyright 2012 by ESPGHAN and NASPGHAN


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