Caspase-1 inhibition attenuates activation of BV2 microglia induced by LPS-treated RAW264.7 macrophages

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.