SCOPE: In this study, the effects of lutein on neuroinflammation in lipopolysaccharide (LPS)-activated BV-2 microglia were investigated. METHODS AND RESULTS: The production of proinflammatory cytokines tumor necrosis factor-α, interleukin-1β, and nitric oxide was measured in culture medium using enzyme immunoassay and Griess reagent, respectively. The expression of proteins was determined using Western blot. Pretreatment with lutein (50 μM) prior to LPS (1 μg/mL, 12 h) stimulation resulted in a significant inhibition of inducible nitric oxide synthase and cyclooxygenase-2 expression, as well as tumor necrosis factor-α, interleukin-1β, and nitric oxide production (p < 0.05). Further experiments demonstrated that lutein suppressed LPS-induced NF-κB activation by inhibiting the phosphorylation of p38 kinase, c-Jun N-terminal kinase (JNK), and Akt kinase (p < 0.05). Moreover, lutein markedly quenched reactive oxygen species and promoted antioxidant protein expression including heme oxygenase-1 and NAD(P)H: quinone oxidoreductase by enhancing the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) mediated NF-E2-related factor 2 (Nrf2) activation (p < 0.05). CONCLUSION: These results suggest that lutein attenuates neuroinflammation in LPS-activated BV-2 microglia partly through inhibiting p38-, JNK-, and Akt-stimulated NF-κB activation and promoting ERK-induced Nrf2 activation, suggesting that lutein has great potential as a nutritional preventive strategy in inflammation-related neurodegenerative disorders.
SCOPE: In this study, the effects of lutein on neuroinflammation in lipopolysaccharide (LPS)-activated BV-2 microglia were investigated. METHODS AND RESULTS: The production of proinflammatory cytokines tumor necrosis factor-α, interleukin-1β, and nitric oxide was measured in culture medium using enzyme immunoassay and Griess reagent, respectively. The expression of proteins was determined using Western blot. Pretreatment with lutein (50 μM) prior to LPS (1 μg/mL, 12 h) stimulation resulted in a significant inhibition of inducible nitric oxide synthase and cyclooxygenase-2 expression, as well as tumor necrosis factor-α, interleukin-1β, and nitric oxide production (p < 0.05). Further experiments demonstrated that lutein suppressed LPS-induced NF-κB activation by inhibiting the phosphorylation of p38 kinase, c-Jun N-terminal kinase (JNK), and Akt kinase (p < 0.05). Moreover, lutein markedly quenched reactive oxygen species and promoted antioxidant protein expression including heme oxygenase-1 and NAD(P)H: quinone oxidoreductase by enhancing the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) mediated NF-E2-related factor 2 (Nrf2) activation (p < 0.05). CONCLUSION: These results suggest that lutein attenuates neuroinflammation in LPS-activated BV-2 microglia partly through inhibiting p38-, JNK-, and Akt-stimulated NF-κB activation and promoting ERK-induced Nrf2 activation, suggesting that lutein has great potential as a nutritional preventive strategy in inflammation-related neurodegenerative disorders.
Authors: Martha Clare Morris; Yamin Wang; Lisa L Barnes; David A Bennett; Bess Dawson-Hughes; Sarah L Booth Journal: Neurology Date: 2017-12-20 Impact factor: 9.910