Differential requirement for the activation of the inflammasome for processing and release of IL-1β in monocytes and macrophages
Differential requirement for the activation of the inflammasome for processing and release of IL-1β in monocytes and macrophages
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DOI：
10.1182/blood-2008-03-146720
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发表时间：
2009-03-05
期刊：
影响因子：
20.3
通讯作者：
Dinarello, Charles A.
中科院分区：
文献类型：
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作者：
Netea, Mihai G.;Nold-Petry, Claudia A.;Dinarello, Charles A.
前白介素1β的处理依赖于caspase-1的激活。Toll样受体(TLR)配体能否单独激活caspase-1释放白介素1-β(IL-1β)一直存在争议。在这里，我们证明了人血单核细胞在TLR2或TLR4配体一次性刺激后释放经过处理的IL-1β，这是由于结构性激活的caspase-1和内源性三磷酸腺苷的释放所致。Caspase-1的结构性激活依赖于炎症体成分、含有caspase募集域的凋亡相关斑点样蛋白(ASC)和NALP3，但在单核细胞中，caspase-1的激活与病原体相关的分子模式识别无关。相比之下，巨噬细胞不能单独通过TLR配体处理和释放IL-1β，需要第二次三磷酸腺苷刺激。我们得出结论，IL-1β的产生在单核细胞和巨噬细胞中受到不同的调节，这反映了它们在宿主防御和炎症中的不同功能。(血。2009；113：2324-2335)
The processing of pro-interleukin-1 beta depends on activation of caspase-1. Controversy has arisen whether Toll-like receptor (TLR) ligands alone can activate caspase-1 for release of interleukin-1 beta (IL-1 beta). Here we demonstrate that human blood monocytes release processed IL-1 beta after a one-time stimulation with either TLR2 or TLR4 ligands, resulting from constitutively activated caspase-1 and release of endogenous adenosine triphosphate. The constitutive activation of caspase-1 depends on the inflammasome components, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and NALP3, but in monocytes caspase-1 activation is uncoupled from pathogen-associated molecular pattern recognition. In contrast, macrophages are unable to process and release IL-1 beta solely by TLR ligands and require a second adenosine triphosphate stimulation. We conclude that IL-1 beta production is differentially regulated in monocytes and macrophages, and this reflects their separate functions in host defense and inflammation. (Blood. 2009; 113: 2324-2335)