The pivotal role of p38 and NF-κB signal pathways in the maturation of human monocyte-derived dendritic cells stimulated by streptococcal agent OK-432
The pivotal role of p38 and NF-κB signal pathways in the maturation of human monocyte-derived dendritic cells stimulated by streptococcal agent OK-432
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p38 和 NF-kappaB 信号通路在链球菌制剂 OK-432 刺激的人单核细胞衍生树突状细胞成熟中的关键作用。
DOI：
10.1016/j.imbio.2008.10.008
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发表时间：
2009-05-01
期刊：
影响因子：
2.8
通讯作者：
Xia, Jian-chuan
中科院分区：
文献类型：
--
作者：
Pan, Ke;Wang, Hui;Xia, Jian-chuan
OK-432是一种链球菌制剂，已被证明是诱导人单核细胞来源的树突状细胞成熟的有效激活剂。在此过程中，Toll样受体4的激活起着重要作用。然而，参与的信号通路尚未完全了解。在本研究中，我们研究了OK-432诱导人单核细胞来源的DC（MoDC）成熟的潜在机制。我们观察到OK-432激活了未成熟MoDC的p38 MAPK和NF-κ B通路，同时上调了成熟标志物CD 80、CD 83、CD 86和HLA-DR的表面表达，增加了TNF-α、IL-12和趋化因子IP-10的分泌。此外，T细胞刺激能力也增强。用p38通路抑制剂S13203580或NF-κ B通路抑制剂BAY-117082处理可抑制OK-432刺激的MoDC的成熟。而用SP 600125阻断JNK通路或用PD 98059阻断ERK通路对OK-432诱导的DCs成熟无影响。综上所述，我们的数据表明，OK-432诱导的DCs成熟至少部分是由于p38和NF-κ B通路的激活。(C)2008年Elsevier GmbH。All rights reserved.
OK-432, a streptococcal preparation, has been shown as an effective activator to induce human monocyte-derived dendritic cells maturation. During this process, the activation of Toll-like receptor 4 plays an important role. However, the signaling pathway involved in has not been fully understood. In the present study, we investigated the underlying mechanisms, by which OK-432 induced maturation of human monocyte-derived DCs (MoDCs). We observed that exposure of immature MoDCs to OK-432 activated the p38 MAPK and NF-kappa B pathway, accompanied up-regulated the surface expression of maturation markers CD80, CD83, CD86 and HLA-DR, increased secretion of TNF-alpha, IL-12 and chemokine, IP-10. In addition, T cells stimulatory capacity was also enhanced. The maturation of MoDCs stimulated by OK-432 was inhibited by treatment with p38 pathway inhibitor, S13203580, or NF-kappa B pathway inhibitor, BAY-117082. Whereas, blocking of JNK pathway with SP600125 or ERK pathway with PD98059 did not influence OK-432-induced DCs maturation. Taken together, our data indicated that OK-432-induced DCs maturation was due, at least partly to the activation of p38 and NF-kappa B pathway. (C) 2008 Elsevier GmbH. All rights reserved.