TGF-β activity in cow milk and fermented milk products: An in vitro bioassay with oral fibroblasts

OBJECTIVE Milk is a rich source of transforming growth factor (TGF)-β which supports intestinal mucosal homeostasis of infants. Milk may also have beneficial effects on the integrity of the oral cavity, its being part of the gastrointestinal tract. However, it is unclear if milk and fermented milk products provoke a TGF-β response in oral cells. MATERIAL AND METHODS Human gingival fibroblasts were exposed to pasteurized cow milk, yoghurt, sour milk, buttermilk and whey, followed by a reverse transcriptase polymerase chain reaction of the TGF-β target genes interleukin11 (IL11), proteoglycan4 (PRG4), and NADPH oxidase 4 (NOX4). Immunoassays were performed for IL11 and TGF-β in cell culture supernatant and milk products, respectively. Signaling was investigated with the TGF-β receptor type I kinase inhibitor SB431542. RESULTS We report here that pasteurized cow milk and the aqueous fractions of yoghurt, sour milk, buttermilk and whey enhanced the expression of IL11, NOX4 and PRG4 in gingival fibroblasts. Moreover, IL11 protein levels in the respective supernatant were significantly increased. Cow milk, yoghurt, sour milk and buttermilk contain approximately 1-2 ng TGF-β1, whereas active TGF-β1 is hardly detectable in whey. SB431542 reduced the response of gingival fibroblasts to pasteurized cow milk and fermented milk products based on IL11 release into the supernatant. CONCLUSIONS These results demonstrate that gingival fibroblasts respond to pasteurized cow milk and to fermented milk products with an increased expression of TGF-β target genes.