Transforming Growth Factor-β Activity in Commercially Available Pasteurized Cow Milk Provides Protection against Inflammation in Mice

Abstract

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