NADPH oxidase derived reactive oxygen species are involved in human neutrophil IL-1β secretion but not in inflammasome activation
NADPH oxidase derived reactive oxygen species are involved in human neutrophil IL-1β secretion but not in inflammasome activation
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DOI：
10.1002/eji.201243089
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发表时间：
2013-12-01
影响因子：
5.4
通讯作者：
Trevani, Analia S.
中科院分区：
文献类型：
--
作者：
Laura Gabelloni, Maria;Sabbione, Florencia;Trevani, Analia S.
中性粒细胞是急性炎症反应中的重要参与者。在刺激后，中性粒细胞激活NADPH氧化酶，产生一系列活性氧（ROS）。白细胞介素-1 β（IL-1）是一种主要的促炎细胞因子，作为前体合成，必须经过蛋白水解加工才能具有生物活性。ROS在IL-1加工中的作用仍然存在争议，并且以前没有在中性粒细胞中进行过研究。我们在这里报告，IL-1在人类中性粒细胞的加工是依赖于半胱天冬酶-1和丝氨酸蛋白酶弹性蛋白酶和/或蛋白酶3。NADPH氧化酶缺陷型中性粒细胞激活半胱天冬酶-1，并且没有表现出NALP 3表达的差异，这表明ROS既不是炎性小体激活所需的，也不是其引发所需的，如巨噬细胞所报道的那样。引人注目的是，活性氧产生相反的作用，对IL-1的加工和分泌，而活性氧负控制caspase-1的活性，如单核吞噬细胞，活性氧被发现是必要的成熟IL-1的出口出细胞，以前从未描述的作用。ROS介导的中性粒细胞IL-1分泌的复杂调节可能构成了控制IL-1依赖性炎症过程的生理机制，其中中性粒细胞起着至关重要的作用。
Neutrophils are essential players in acute inflammatory responses. Upon stimulation, neutrophils activate NADPH oxidase, generating an array of reactive oxygen species (ROS). Interleukin-1 beta (IL-1) is a major proinflammatory cytokine synthesized as a precursor that has to be proteolytically processed to become biologically active. The role of ROS in IL-1 processing is still controversial and has not been previously studied in neutrophils. We report here that IL-1 processing in human neutrophils is dependent on caspase-1 and on the serine proteases elastase and/or proteinase 3. NADPH oxidase deficient neutrophils activated caspase-1 and did not exhibit differences in NALP3 expression, indicating that ROS are neither required for inflammasome activation nor for its priming, as has been reported for macrophages. Strikingly, ROS exerted opposite effects on the processing and secretion of IL-1; whereas ROS negatively controlled caspase-1 activity, as reported in mononuclear phagocytes, ROS were found to be necessary for the exportation of mature IL-1 out of the cell, a role never previously described. The complex ROS-mediated regulation of neutrophil IL-1 secretion might constitute a physiological mechanism to control IL-1-dependent inflammatory processes where neutrophils play a crucial role.