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

作　　者：Yang Pan Bo Shen Qin Gao Jun Zhu Jingde Dong Li Zhang Yingdong Zhang 

机构地区：[1]Department of Neurology, Nanjing First Hospital affiliated to Nanjing Medical University, Nanjing, Jiangsu 210006, China [2]Department of Geriatrics, Nanjing Brain Hospital affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, China

出　　处：《The Journal of Biomedical Research》2016年第3期225-233,共9页生物医学研究杂志（英文版）

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)

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.

关 键 词：peripheral inflammation NEUROINFLAMMATION neurodegenerative diseases NLRP3 inflammasome CASPASE-1 

分 类 号：R741[医药卫生—神经病学与精神病学]