Differential effects of the Toll-like receptor 2 agonists, PGN and Pam3CSK4 on anti-IgE induced human mast cell activation.
Differential effects of the Toll-like receptor 2 agonists, PGN and Pam3CSK4 on anti-IgE induced human mast cell activation.
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Toll 样受体 2 激动剂、PGN 和 Pam3CSK4 对抗 IgE 诱导的人肥大细胞激活的不同作用
DOI：
10.1371/journal.pone.0112989
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Lau HY
中科院分区：
文献类型：
--
作者：
Yu Y;Yip KH;Tam IY;Sam SW;Ng CW;Zhang W;Lau HY
肥大细胞在变态反应和炎症的发病机制中是关键的。除了涉及IgE高亲和力受体（FcεRI）交联的经典IgE依赖性机制外，肥大细胞还被Toll样受体（TLR）激活，Toll样受体是先天免疫的中心。在这项研究中，我们证明了LAD 2细胞（一种人肥大细胞系）对抗IgE的反应在TLR 2激动剂肽聚糖（PGN）和三棕榈酰-S-甘油-Cys-（Lys）4（Pam 3CSK 4）的存在下发生了改变。PGN和Pam 3CSK 4预处理可抑制抗IgE诱导的钙动员和脱颗粒，而不下调FcεRI的表达。当TLR 2激动剂与抗IgE同时加入时，Pam 3CSK 4而不是PGN与抗IgE协同作用以释放IL-8。对肥大细胞信号传导中涉及的关键酶的抑制剂的研究表明，由Pam 3CSK 4和抗IgE诱导的IL-8的协同释放涉及ERK和钙调神经磷酸酶信号传导级联。PGN和Pam 3CSK 4对抗IgE诱导的肥大细胞活化的不同调节作用提示TLR 2与TLR 1或TLR 6的二聚体化对FcεRI介导的人肥大细胞活化具有不同的调节作用。
Mast cells are pivotal in the pathogenesis of allergy and inflammation. In addition to the classical IgE-dependent mechanism involving crosslinking of the high-affinity receptor for IgE (FcεRI), mast cells are also activated by Toll-like receptors (TLRs) which are at the center of innate immunity. In this study, we demonstrated that the response of LAD2 cells (a human mast cell line) to anti-IgE was altered in the presence of the TLR2 agonists peptidoglycan (PGN) and tripalmitoyl-S-glycero-Cys-(Lys)4 (Pam3CSK4). Pretreatment of PGN and Pam3CSK4 inhibited anti-IgE induced calcium mobilization and degranulation without down-regulation of FcεRI expression. Pam3CSK4 but not PGN acted in synergy with anti-IgE for IL-8 release when the TLR2 agonist was added simultaneously with anti-IgE. Studies with inhibitors of key enzymes implicated in mast cell signaling revealed that the synergistic release of IL-8 induced by Pam3CSK4 and anti-IgE involved ERK and calcineurin signaling cascades. The differential modulations of anti-IgE induced mast cell activation by PGN and Pam3CSK4 suggest that dimerization of TLR2 with TLR1 or TLR6 produced different modulating actions on FcεRI mediated human mast cell activation.