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TGF-β2 induces maturation of immature human intestinal epithelial cells and inhibits inflammatory cytokine responses induced via the NF-κB pathway.
J Pediatr Gastroenterol Nutr. 2012 May; 54(5):630-8.JP

Abstract

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.

Authors+Show Affiliations

Division of Pediatric Gastroenterology, Massachusetts General Hospital for Children, Charlestown, MA 02192-4404, USA. samrau@utu.fiNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22067113

Citation

Rautava, Samuli, et al. "TGF-β2 Induces Maturation of Immature Human Intestinal Epithelial Cells and Inhibits Inflammatory Cytokine Responses Induced Via the NF-κB Pathway." Journal of Pediatric Gastroenterology and Nutrition, vol. 54, no. 5, 2012, pp. 630-8.
Rautava S, Lu L, Nanthakumar NN, et al. TGF-β2 induces maturation of immature human intestinal epithelial cells and inhibits inflammatory cytokine responses induced via the NF-κB pathway. J Pediatr Gastroenterol Nutr. 2012;54(5):630-8.
Rautava, S., Lu, L., Nanthakumar, N. N., Dubert-Ferrandon, A., & Walker, W. A. (2012). TGF-β2 induces maturation of immature human intestinal epithelial cells and inhibits inflammatory cytokine responses induced via the NF-κB pathway. Journal of Pediatric Gastroenterology and Nutrition, 54(5), 630-8. https://doi.org/10.1097/MPG.0b013e31823e7c29
Rautava S, et al. TGF-β2 Induces Maturation of Immature Human Intestinal Epithelial Cells and Inhibits Inflammatory Cytokine Responses Induced Via the NF-κB Pathway. J Pediatr Gastroenterol Nutr. 2012;54(5):630-8. PubMed PMID: 22067113.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TGF-β2 induces maturation of immature human intestinal epithelial cells and inhibits inflammatory cytokine responses induced via the NF-κB pathway. AU - Rautava,Samuli, AU - Lu,Lei, AU - Nanthakumar,N Nanda, AU - Dubert-Ferrandon,Alix, AU - Walker,W Allan, PY - 2011/11/10/entrez PY - 2011/11/10/pubmed PY - 2012/9/7/medline SP - 630 EP - 8 JF - Journal of pediatric gastroenterology and nutrition JO - J Pediatr Gastroenterol Nutr VL - 54 IS - 5 N2 - 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. SN - 1536-4801 UR - https://www.unboundmedicine.com/medline/citation/22067113/TGF_β2_induces_maturation_of_immature_human_intestinal_epithelial_cells_and_inhibits_inflammatory_cytokine_responses_induced_via_the_NF_κB_pathway_ L2 - https://doi.org/10.1097/MPG.0b013e31823e7c29 DB - PRIME DP - Unbound Medicine ER -