Betalactam antibiotics affect human dendritic cells maturation through MAPK/NF-kB systems. Role in allergic reactions to drugs
Betalactam antibiotics affect human dendritic cells maturation through MAPK/NF-kB systems. Role in allergic reactions to drugs
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DOI：
10.1016/j.taap.2015.08.001
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发表时间：
2015-11-01
影响因子：
3.8
通讯作者：
Mayorga, Cristobalina
中科院分区：
文献类型：
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作者：
Lopez, Soledad;Gomez, Enrique;Mayorga, Cristobalina
导致易感患者药物过敏的机制，特别是与T细胞介导的药物超敏反应相关的机制尚不清楚。药物过敏反应中的一个关键事件是树突状细胞（DC）的成熟过程。虽然阿莫西林（AX）已被报道与AX诱导的迟发型超敏反应患者的DC相互作用并使其成熟，但与AX介导的DC成熟相关的细胞信号通路尚未阐明。我们试图确定MAPK和NF-κ B通路对AX诱导的DC成熟和功能状态的作用。为此，在来自AX延迟过敏患者和耐受受试者的单核细胞衍生的DC中，我们分析了p38 MAPK、JNK和ERK信号传导和NF-κ B、成熟标志物以及由AX刺激的DC驱动的内吞和同种异体刺激能力的激活模式。我们的数据显示，AX诱导过敏患者DC中三种MAPK和活化的NF-κ B的磷酸化水平增加。此外，这些途径的抑制防止了AX诱导的表面分子的上调。此外，我们观察到，同种异体刺激能力和内吞下调AX刺激的DC从过敏患者依赖于JNK和NF-κ B活性。综上所述，我们的数据首次揭示了AX延迟过敏患者DC成熟的主要信号通路。(C)2015 Elsevier Inc. All rights reserved.
The mechanisms leading to drug allergy in predisposed patients, especially those related to T-cell-mediated drug hypersensitivity, are not well understood. A key event in allergic reactions to drugs is the maturation process undergone by dendritic cells (DCs). Although amoxicillin (AX) has been reported to interact and maturate DCs from patients with AX-induced delayed-type hypersensitivity, the cell signaling pathways related to AX-mediated DC maturation have not been elucidated. We sought to determine the role of the MAPK and NF-KB pathways on AX-induced DC maturation and functional status. For that purpose, in monocyte-derived-DCs from AX-delayed allergic patients and tolerant subjects, we analyzed the activation pattern of p38MAPK, JNK, and ERK signaling and the NF-KB, maturation markers as well as endocytosis and allostimulatory capacities driven by AX-stimulated-DCs. Our data reveal that AX induces an increase in the phosphorylation levels of the three MAPKsand activated NF-KB in DCs from allergic patients. Moreover, the inhibition of these pathways prevents the up-regulation of surface molecules induced by AX. Additionally, we observed that the allostimulatory capacity and the endocytosis down-regulation in AX-stimulated-DCs from allergic patients depend on JNK and NF-KB activities. Taken together, our data shed light for the first time on the main signaling pathways involved in DC maturation from AX-delayed allergic patient. (C) 2015 Elsevier Inc. All rights reserved.