A positive effect of selenoprotein on mammary gland: Selenoprotein P stabilizes tight junctions by reducing cell death through inflammation mitigation in mice

Lactational mastitis threatens maternal-infant health and animal husbandry efficiency, with traditional antibiotics limited by milk residues and bacterial resistance. Selenium (Se) regulates inflammation via selenoproteins, but its core effector in mammary inflammation remains unclear. This study investigates the role and mechanism of Se and selenoprotein P (SeP) in LPS-induced mastitis. Tissue pathology, inflammation, apoptosis, and tight junctions (TJs) are assessed via H&E staining, qPCR, Western blot, etc., in mice with varying Se diets (deficient, basal, enriched) subjected to LPS-induced mastitis, and in mouse mammary epithelial cells (MMECs) with SeP silencing or enrichment. Se deficiency exacerbates LPS-induced acinar atrophy, inflammation, NF-κB activation, and release of pro-inflammatory factors (IL-6, IL-1β, TNF-α), while Se enrichment alleviates these effects. SeP, highly expressed in lactating mammary tissue and upregulated by Se, mediates protection through three pathways: inhibiting NF-κB to reduce inflammation, regulating the BAX/BCL2 balance and RIPK1/RIPK3/MLKL pathway to suppress apoptosis and necroptosis, and stabilizing TJ proteins (ZO-1, Occludin, Claudin-1) to repair the blood-milk barrier. In summary, SeP is a core effector of Se in regulating mammary inflammatory injury, maintaining lactational mammary homeostasis via anti-inflammatory, anti-apoptotic, and barrier-protective effects, and provides a new target for mastitis management. • Dietary selenium modulates mammary inflammation: supplement eases LPS damage • Selenoprotein P abounds in lactating mammary tissue, selenium-regulated and stable • Selenoprotein P reduces proinflammatory factors via inhibiting key pathway • Selenoprotein P curbs mammary cell death by blocking death pathway • Selenoprotein P repairs the blood-milk barrier by stabilizing tight junction protein