Cow milk contains a large amount of an immunoregulatory
cytokine,
transforming growth factor-beta (
TGFbeta). The present study investigated whether commercially available pasteurized cow milk retains
TGFbeta activity both in vitro and in vivo. Some commercial cow milk increased
TGFbeta/Smad-responsive reporter activity and induced Smad2 phosphorylation and the transcription of the
TGFbeta/Smad target genes
TGFbeta itself and Smad7 in vitro. Mice treated orally with 500 microL of cow milk containing
TGFbeta (3 microg/L) daily for 2 wk had increased phosphorylation of Smad2 and
TGFbeta and Smad7
mRNA expression in the intestine. These mice also had significantly greater serum
TGFbeta concentrations than the mice treated orally with PBS. Furthermore,
oral administration of 500 microL of cow milk containing
TGFbeta (3 microg/L) daily for 2 wk before the induction of
dextran sodium sulfate colitis and
lipopolysaccharide-induced
endotoxemia ameliorated tissue damage and mortality, respectively, in mice. These in vivo effects of cow milk were abrogated by the simultaneous administration of
TGFbeta type I receptor
kinase inhibitor with the cow milk, and they were not observed after the
oral administration of cow's milk containing little
TGFbeta. In humans, 1 oral challenge of 10 mL/kg cow milk containing
TGFbeta (3 microg/L) increased the plasma
TGFbeta concentrations at 4 h after the challenge. Thus, some commercially available pasteurized cow milk retains
TGFbeta activity, which may be able to provide protection against experimental
colitis and
endotoxemia associated with increased intestinal and circulating
TGFbeta levels.