BACKGROUND: Epidemiologic studies suggest that TGF-beta in breast milk provides protection against allergic disease during infancy. However, it is unclear whether orally administered TGF-beta, such as TGF-beta in human milk, retains and exerts its activity in the intestinal mucosa and can affect immune response (tolerance) to dietary antigens. OBJECTIVE: We sought to determine whether orally administered TGF-beta is biologically active in intestinal mucosa and affects oral tolerance. METHODS: Activity of orally administered TGF-beta in the intestinal mucosa was evaluated by means of in vivo imaging with transgenic mice expressing a Smad-responsive reporter construct (SBE-luc mice), by means of immunohistochemical staining with anti-phosphorylated Smad2 antibody, and by means of real-time RT-PCR analysis of TGF-beta and Smad7 mRNA expression. The effects of orally administered TGF-beta on oral tolerance induction were assessed in mice tolerized by means of high-dose ovalbumin (OVA) feeding. RESULTS: The oral administration of TGF-beta increased Smad-responsive reporter activity in the intestines of SBE-luc mice and induced Smad2 phosphorylation and TGF-beta and Smad7 mRNA expression in the intestines of BALB/c mice. Serum TGF-beta levels were also increased after oral administration of TGF-beta. BALB/c mice treated orally with OVA and TGF-beta showed augmented reduction of OVA-specific IgE and IgG1 antibodies, T-cell reactivity, and immediate-type skin reactions when compared with the mice treated orally with OVA alone. CONCLUSIONS: Orally administered TGF-beta retains sufficient biologic activity in intestinal mucosa and enhances oral tolerance. CLINICAL IMPLICATIONS: Oral administration of TGF-beta might become a potential strategy to prevent allergic diseases, such as food allergy.
BACKGROUND: Epidemiologic studies suggest that TGF-beta in breast milk provides protection against allergic disease during infancy. However, it is unclear whether orally administered TGF-beta, such as TGF-beta in human milk, retains and exerts its activity in the intestinal mucosa and can affect immune response (tolerance) to dietary antigens. OBJECTIVE: We sought to determine whether orally administered TGF-beta is biologically active in intestinal mucosa and affects oral tolerance. METHODS: Activity of orally administered TGF-beta in the intestinal mucosa was evaluated by means of in vivo imaging with transgenic mice expressing a Smad-responsive reporter construct (SBE-luc mice), by means of immunohistochemical staining with anti-phosphorylated Smad2 antibody, and by means of real-time RT-PCR analysis of TGF-beta and Smad7 mRNA expression. The effects of orally administered TGF-beta on oral tolerance induction were assessed in mice tolerized by means of high-dose ovalbumin (OVA) feeding. RESULTS: The oral administration of TGF-beta increased Smad-responsive reporter activity in the intestines of SBE-luc mice and induced Smad2 phosphorylation and TGF-beta and Smad7 mRNA expression in the intestines of BALB/c mice. Serum TGF-beta levels were also increased after oral administration of TGF-beta. BALB/c mice treated orally with OVA and TGF-beta showed augmented reduction of OVA-specific IgE and IgG1 antibodies, T-cell reactivity, and immediate-type skin reactions when compared with the mice treated orally with OVA alone. CONCLUSIONS: Orally administered TGF-beta retains sufficient biologic activity in intestinal mucosa and enhances oral tolerance. CLINICAL IMPLICATIONS: Oral administration of TGF-beta might become a potential strategy to prevent allergic diseases, such as food allergy.
Authors: Christine L M Joseph; Suzanne Havstad; Kevin Bobbitt; Kimberley Woodcroft; Edward M Zoratti; Christian Nageotte; Rana Misiak; Robert Enberg; Charlotte Nicholas; Jerel M Ezell; Dennis R Ownby; Christine Cole Johnson Journal: Pediatr Allergy Immunol Date: 2014-02-13 Impact factor: 6.377
Authors: Penny Van Esterik; Anthony Williams; Mary S Fewtrell; Jules J M Tolboom; Gideon Lack; Martin Penagos Journal: Matern Child Nutr Date: 2010-01 Impact factor: 3.092