IL-1β secretion induced by Aggregatibacter (Actinobacillus) actinomycetemcomitans is mainly caused by the leukotoxin
IL-1β secretion induced by Aggregatibacter (Actinobacillus) actinomycetemcomitans is mainly caused by the leukotoxin
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DOI：
10.1016/j.ijmm.2007.06.005
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发表时间：
2008-07-01
影响因子：
4.1
通讯作者：
Johansson, Anders
中科院分区：
文献类型：
--
作者：
Kelk, Peyman;Claesson, Rolf;Johansson, Anders
Aggregatibacter(放线杆菌)伴生放线菌形成一种白毒素，选择性地裂解灵长类中性粒细胞和单核细胞，并触发早幼粒细胞的凋亡和人类中性粒细胞的脱颗粒。最近，我们发现白斑毒素可引起人巨噬细胞caspase-1的激活和生物活性IL-1β的大量分泌。在这项研究中，我们发现高水平的IL-β与侵袭性牙周炎患者的临床样本中高比例的放线菌相关。为了确定白毒素在细菌诱导的整体IL-1β分泌中的相对贡献，从外周血中分离巨噬细胞，并将其暴露于不同浓度的不同浓度的放线菌伴生活菌株中，这些菌株没有、低或高产生白毒素。用ELISA法和流式细胞仪检测细胞裂解和IL-1β、IL-6、TNF-α和caspase-1水平。白斑毒素是巨噬细胞分泌IL-1β的主要原因，即使在白毒素产量较低的伴生放线杆菌中也是如此。暴露于非白毒菌的巨噬细胞积聚了胞浆中的前IL-1β，这是由二次暴露于白毒细菌而分泌的。综上所述，本研究首次表明放线杆菌在体外诱导人巨噬细胞分泌IL-1β主要是由白毒素引起的。(C)2007年爱思唯尔股份有限公司。版权所有。
Aggregatibacter (Actinobacillus) actinomycetemcomitans forms a leukotoxin that selectively lyses primate neutrophils, monocytes and triggers apoptosis in promyeloic cells and degranulation of human neutrophils. Recently, we showed that the leukotoxin causes activation of caspase-1 and abundant secretion of bio-active IL-1 beta from human macrophages. In this study, we show that high levels of IL-beta correlated with a high proportion of A. actinomycetemeomitans in clinical samples from a patient with aggressive periodontitis. To determine the relative contribution of leukotoxin to the overall bacteria-induced IL-1 beta secretion, macrophages were isolated from peripheral blood and exposed to different concentrations of live A. actinomycetemcomitans strains with either no, low or high production of leukotoxin. Cell lysis and levels of IL-1 beta, IL-6, TNF-alpha and caspase-1 were measured by ELISA and flow cytometry. Leukotoxin was the predominant cause of IL-1 beta secretion from macrophages, even in the A. actinomycetemcomitans strain with low leukotoxin production. Macrophages exposed to non-leukotoxic bacteria accumulated cytosolic pro-IL-1 beta, which was secreted by a secondary exposure to leukotoxic bacteria. In conclusion, the present study shows for the first time that A. actinomyeetemcomitans-induced IL-1 beta secretion from human macrophages in vitro is mainly caused by leukotoxin. (C) 2007 Elsevier GmbH. All rights reserved.