Caspase-1 inhibition attenuates activation of BV2 microglia induced by LPS-treated RAW264.7 macrophages |
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Authors: | Yang Pan Bo Shen Qin Gao Jun Zhu Jingde Dong Li Zhang Yingdong Zhang |
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Institution: | 1.Department of Neurology, Nanjing First Hospital affiliated to Nanjing Medical University, Nanjing, Jiangsu 210006, China2.Department of Geriatrics, Nanjing Brain Hospital affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, China |
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Abstract: | Neuroinflammation has been recognized as a factor in the pathogenesis of neurodegenerative 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 peripheral inflammation, neuroinflammation and neurodegeneration remain unknown. In the present study, we prepared a peripheral inflammation model with lipopolysaccharides (LPS)-stimulated RAW264.7 macrophages to explore its activation on BV2 microglia. We found that LPS induced the production of IL-1β, IL-6 and TNF-α 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-1β, which was suppressed by ZYVAD, a caspase-1 inhibitor. Furthermore, the conditioned medium obtained from LPS-treated RAW264.7 macrophages activated BV2 microglia, stimulating the release of IL-1β, IL-6 and TNF-α 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. |
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Keywords: | peripheral inflammation neuroinflammation neurodegenerative diseases NLRP3 inflammasome caspase-1 |
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