Orally administered TGF-beta is biologically active in the intestinal mucosa and enhances oral tolerance.
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.


CONCLUSIONS
Oral administration of TGF-beta might become a potential strategy to prevent allergic diseases, such as food allergy.
Ando
Takashi
T
Department of Immunology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
Hatsushika
Kyosuke
K
Wako
Masanori
M
Ohba
Tetsuro
T
Koyama
Kensuke
K
Ohnuma
Yuko
Y
Katoh
Ryohei
R
Ogawa
Hideoki
H
Okumura
Ko
K
Luo
Jian
J
Wyss-Coray
Tony
T
Nakao
Atsuhito
A
D000284:Administration, Oral; D000818:Animals; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010766:Phosphorylation; D051899:Smad2 Protein / Q000378:metabolism; D051906:Smad7 Protein / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*
D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051906:Smad7 Protein; C497807:Smad7 protein, mouse; D016212:Transforming Growth Factor beta; D010047:Ovalbumin