β-Amyloid(1-42)(Aβ_(42))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 Aβ_(42)-ind...β-Amyloid(1-42)(Aβ_(42))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 Aβ_(42)-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 Aβ_(42)-induced inflammation in BV-2 microglia using various techniques,including cell morphology analysis,immunofluorescence staining,ELISA,q RT-PCR,and Western blot assays.The results demonstrated that Aβ_(42)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,Aβ_(42)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 Aβ_(42)-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.展开更多
基金the financial support received from the Science and Technology Planning Project of Sichuan Province(Jiebangguashuai Project)(2023YFN0101)。
文摘β-Amyloid(1-42)(Aβ_(42))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 Aβ_(42)-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 Aβ_(42)-induced inflammation in BV-2 microglia using various techniques,including cell morphology analysis,immunofluorescence staining,ELISA,q RT-PCR,and Western blot assays.The results demonstrated that Aβ_(42)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,Aβ_(42)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 Aβ_(42)-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.
