부산대학교 도서관

During the lactation cycle of the bovine mammary gland, autophagy is induced in bovine mammary epithelial cells (BMECs) as a cellular homeostasis and survival mecha-nism. Interferon gamma (IFN-) is an important antiproliferative and apoptogenic factor that has been shown to induce autophagy in multiple cell lines in vitro. However, it remains unclear whether IFN- can induce autophagy and whether autophagy affects milk synthesis in BMECs. To understand whether IFN- affects milk synthesis, we isolated and purified primary BMECs and investigated the effect of IFN- on milk synthesis in primary BMECs in vitro. The results showed that IFN- significantly inhibits milk synthesis and that autophagy was clearly induced in primary BMECs in vitro within 24 h. Interestingly, autophagy was observed following IFN- treatment, and the inhibition of autophagy can improve milk protein and milk fat syn-thesis. Conversely, upregulation of autophagy decreased milk synthesis. Furthermore, mechanistic analysis con-firmed that IFN- mediated autophagy by depleting argi-nine and inhibiting the general control nonderepressible-2 kinase (GCN2)/eukaryotic initiation factor 2 (eIF2) signaling pathway in BMECs. Then, it was found that arginine supplementation could attenuate IFN--induced autophagy and recover milk synthesis to some extent. These findings may not only provide a novel measure for preventing the IFN--induced decrease in milk quality but also a useful therapeutic approach for IFN--associated breast diseases in other animals and humans.