TY - JOUR
T1 - IL-1β directly inhibits milk lipid production in lactating mammary epithelial cells concurrently with enlargement of cytoplasmic lipid droplets
AU - Matsunaga, Kota
AU - Tsugami, Yusaku
AU - Kumai, Aogu
AU - Suzuki, Takahiro
AU - Nishimura, Takanori
AU - Kobayashi, Ken
N1 - Funding Information:
We are deeply grateful to Prof. Fumio Nakamura, Laboratory of Animal By-Product Science, Research Faculty of Agriculture, Hokkaido University, for fine instruction on immunohistochemistry techniques and useful discussions. This work was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science ( KAKENHI , 2645044104 ).
PY - 2018/9/15
Y1 - 2018/9/15
N2 - Mammary epithelial cells (MECs) in lactating mammary glands produce milk lipid, which provides a large percentage of calories and bioactive lipids for appropriate infant growth. However, secreted milk lipid is often reduced concurrently with increases in IL-1β IL-6, and TNF-α in mammary glands with mastitis. In this study, we investigated whether those cytokines directly influenced lipid production and secretion. A lactating MEC culture model with high lipid production ability was prepared by culture with oleic acid. TNF-α IL-1β and IL-6 differentially affected lipid production and secretion in lactating MECs. In particular, IL-1β treatment significantly reduced amounts of secreted triglycerides by 97% compared with the control concurrently with enlargement of cytoplasmic lipid droplets in MECs. IL-1β also decreased mRNA expression of Fabp3 and Srebp1 and the amount of aquaporin 3, GLUT-1 and adipophilin in the milk lipid production pathway. Furthermore, IL-1β inactivated STAT5 and glucocorticoid signaling to induce milk production in MECs, whereas STAT3 and NFκB signaling was activated. IL-1β induced mRNA expression of IL-6 and TNF-α in MECs. Therefore, we suggest that IL-1β is a key inhibitor of lipid production and secretion in lactating MECs.
AB - Mammary epithelial cells (MECs) in lactating mammary glands produce milk lipid, which provides a large percentage of calories and bioactive lipids for appropriate infant growth. However, secreted milk lipid is often reduced concurrently with increases in IL-1β IL-6, and TNF-α in mammary glands with mastitis. In this study, we investigated whether those cytokines directly influenced lipid production and secretion. A lactating MEC culture model with high lipid production ability was prepared by culture with oleic acid. TNF-α IL-1β and IL-6 differentially affected lipid production and secretion in lactating MECs. In particular, IL-1β treatment significantly reduced amounts of secreted triglycerides by 97% compared with the control concurrently with enlargement of cytoplasmic lipid droplets in MECs. IL-1β also decreased mRNA expression of Fabp3 and Srebp1 and the amount of aquaporin 3, GLUT-1 and adipophilin in the milk lipid production pathway. Furthermore, IL-1β inactivated STAT5 and glucocorticoid signaling to induce milk production in MECs, whereas STAT3 and NFκB signaling was activated. IL-1β induced mRNA expression of IL-6 and TNF-α in MECs. Therefore, we suggest that IL-1β is a key inhibitor of lipid production and secretion in lactating MECs.
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U2 - 10.1016/j.yexcr.2018.06.038
DO - 10.1016/j.yexcr.2018.06.038
M3 - Article
C2 - 29966663
AN - SCOPUS:85049323710
VL - 370
SP - 365
EP - 372
JO - Experimental Cell Research
JF - Experimental Cell Research
SN - 0014-4827
IS - 2
ER -