TY  - JOUR
AU  - Li, Dan
AU  - Mu, Xinxin
AU  - Ma, Ying
AU  - Lu, Weihong
AU  - Wang, Rongchun
PY  - 2025
TI  - The inhibitory effects and mechanisms of milk-derived MFG-E8 on Aβ-induced inflammatory responses in BV-2 microglia
JO  - Food Science and Human Wellness
SN  - 2097-0765
SP  - 9250621
VL  - 14
IS  - 10
AB  - β-Amyloid (1-42) (Aβ42) can induce excessive activation of microglia, resulting in exacerbated neuroinflammation and neuronal damage. Milk fat globule-epidermal growth factor-8 (MFG-E8) is known to regulate Aβ42-induced neurotoxicity and inflammatory responses via multiple signaling pathways. However, insufficient secretion of endogenous MFG-E8 may lead to autoimmunity in the central nervous system and the accumulation of apoptotic cells. In this study, we systematically investigated the inhibitory effects and potential mechanisms of exogenously administered milk-derived MFG-E8 (M-MFG-E8) on Aβ42-induced inflammation in BV-2 microglia using various techniques, including cell morphology analysis, immunofluorescence staining, ELISA, qRT-PCR, and Western blot assays. The results demonstrated that Aβ42 significantly increased the expression levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in BV-2 microglia, whereas treatment with M-MFG-E8 effectively reversed these inflammatory responses. Furthermore, Aβ42 stimulation increased the secretion of pro-inflammatory cytokines (TNF-α, IL-1β) and the expression of the M1 marker cluster of differentiation 86 (CD86), while suppressing the anti-inflammatory factors (arginase-1 (Arg-1), interleukin-10 (IL-10)) and the M2 marker cluster of differentiation 206 (CD206) in microglia. In contrast, M-MFG-E8 treatment promoted the polarization of microglia from the M1 to the M2 phenotype. Notably, M-MFG-E8 also inhibited the Aβ42-induced upregulation of CD68, whereas M-MFG-E8 alone did not elicit this effect. Finally, our findings suggest that exogenous M-MFG-E8 may exert anti-inflammatory actions through the modulation of the NF-κB and PI3K/Akt pathways, providing new insights into neuronal cell repair and the development of functional foods.
UR  - https://doi.org/10.26599/FSHW.2025.9250621
DO  - 10.26599/FSHW.2025.9250621