摘要
Neuroinflammation has been recognized as a factor in the pathogenesis ofneurodegenerative diseases. Emerging evidence suggests that peripheral inflammation, besides neuroinflammation, functions as a modulator of disease progression and neuropathology in several neurodegenerative diseases. However, detailed correlations among pe- ripheral inflammation, neuroinflammation and neurodegeneration remain unknown. In the present study, we pre- pared a peripheral inflammation model with lipopolysaccharides （LPS）-stimulated RAW264.7 macrophages to ex- plore its activation on BV2 microglia. We found that LPS induced the production of IL-1β, IL-6 and TNF-a in the culture medium of RAW264.7 macrophages. We further showed that LPS plus ATP activated inflammasome, evidenced by the upregulation of caspase-1 and IL-113, which was suppressed by ZYVAD, a caspase-1 inhibitor. Furthermore, the conditioned medium obtained from LPS-treated RAW264.7 macrophages activated BV2 micro- glia, stimulating the release of IL-1β, IL-6 and TNF-a from BV2 cells. ZYVAD pretreatment markedly suppressed BV2 microglia activation induced by RAW264.7 cells conditioned medium. Taken together, our study indicates that macrophage-mediated peripheral inflammation subsequently evokes neuroinflammation and may aggravate neural damage. Inflammasome and caspase- 1 may be potential targets for modulating systemic inflammatory responses in neurodegenerative diseases.
Neuroinflammation has been recognized as a factor in the pathogenesis ofneurodegenerative diseases. Emerging evidence suggests that peripheral inflammation, besides neuroinflammation, functions as a modulator of disease progression and neuropathology in several neurodegenerative diseases. However, detailed correlations among pe- ripheral inflammation, neuroinflammation and neurodegeneration remain unknown. In the present study, we pre- pared a peripheral inflammation model with lipopolysaccharides （LPS）-stimulated RAW264.7 macrophages to ex- plore its activation on BV2 microglia. We found that LPS induced the production of IL-1β, IL-6 and TNF-a in the culture medium of RAW264.7 macrophages. We further showed that LPS plus ATP activated inflammasome, evidenced by the upregulation of caspase-1 and IL-113, which was suppressed by ZYVAD, a caspase-1 inhibitor. Furthermore, the conditioned medium obtained from LPS-treated RAW264.7 macrophages activated BV2 micro- glia, stimulating the release of IL-1β, IL-6 and TNF-a from BV2 cells. ZYVAD pretreatment markedly suppressed BV2 microglia activation induced by RAW264.7 cells conditioned medium. Taken together, our study indicates that macrophage-mediated peripheral inflammation subsequently evokes neuroinflammation and may aggravate neural damage. Inflammasome and caspase- 1 may be potential targets for modulating systemic inflammatory responses in neurodegenerative diseases.
基金
supported in part by Nanjing Medical Science and Technology Development Foundation(No.ZKX12037,No.YKX13129)
in part by National Natural Science Foundation of China(No.81271418)
