Cyclic AMP suppresses TGF-β-mediated adaptive Tregs differentiation through inhibiting the activation of ERK and JNK
Cyclic AMP suppresses TGF-β-mediated adaptive Tregs differentiation through inhibiting the activation of ERK and JNK
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DOI：
10.1016/j.cellimm.2013.08.006
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发表时间：
2013-09-01
影响因子：
4.3
通讯作者：
Zhang, Jiyan
中科院分区：
文献类型：
--
作者：
Cao, Junxia;Zhang, Xueying;Zhang, Jiyan
第二信使cAMP参与许多细胞活动的调节，部分是通过调节MAPK通路。CAMP在转化生长因子-β介导的适应性树突状细胞分化中的作用仍不清楚。在这项工作中，我们表明，cAMP抑制小鼠CD4+T细胞的抗原非特异性增殖，而不显著促进细胞凋亡。此外，cAMP抑制转化生长因子β诱导的叉头转录因子Foxp3的表达。6-MB-cAMP是一种PKA的位点选择性激活剂，它模拟了cAMP在转化生长因子-β诱导的Foxp3表达中的作用。进一步研究发现，转化生长因子-β可激活ERK和JNK，但不能激活p38。CAMP和6-MB-cAMP分别以转录非依赖和转录依赖的方式阻断转化生长因子-β诱导的ERK和JNK的激活。由于在这一过程中直接抑制ERK或JNK活性的作用与cAMP相似，我们的工作提示cAMP至少部分地通过抑制ERK和JNK的激活来抑制转化生长因子-β介导的适应性Tregs分化。(C)2013爱思唯尔有限公司。保留所有权利。
The second messenger cAMP is involved in the regulation of many cellular activities partially through modulating the MAPK pathways. The role of cAMP in TGF-beta-mediated adaptive Tregs differentiation remains elusive. In this work, we show that cAMP inhibits antigen-nonspecific proliferation of murine CD4+ T cells without significant promotion of apoptosis. Moreover, cAMP suppresses TGF-beta-induced expression of forkhead transcription factor Foxp3. 6-MB-cAMP, a site-selective activator of PKA, mimics the role of cAMP in TGF-beta-induced Foxp3 expression. Further exploration reveals that TGF-beta activates ERK and JNK, but not p38. cAMP and 6-MB-cAMP block TGF-beta-induced activation of ERK and JNK through transcription-independent manner and transcription-dependent manner, respectively. Since direct inhibition of ERK or JNK activity mimics the effects of cAMP during this process, our work suggests that cAMP suppresses TGF-beta-mediated adaptive Tregs differentiation through, at least partially, inhibiting the activation of ERK and JNK. (C) 2013 Elsevier Ltd. All rights reserved.