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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >Cholera toxin enhances interleukin‐17A production in both CD4 + + and CD8 + + cells via a cAMP/protein kinase A‐mediated interleukin‐17A promoter activation
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Cholera toxin enhances interleukin‐17A production in both CD4 + + and CD8 + + cells via a cAMP/protein kinase A‐mediated interleukin‐17A promoter activation

机译：霍乱毒素通过CAMP /蛋白激酶A介导的白细胞介素-17a启动子活化增强CD4 ++和CD8 + +细胞中的白细胞介素-17A产生

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Summary Cholera toxin (CT) is a bacterial component that increases intracellular cAMP levels in host cells and suppresses T‐cell activation. Recently, CT was reported to induce T helper type 17‐skewing dendritic cells and activate interleukin‐17A (IL‐17A) production in CD4 + T cells through a cAMP‐dependent pathway. However, the underlying mechanism by which cAMP regulates IL‐17A production in T cells is not completely defined. In this study, we took advantage of a small molecule protein kinase A (PKA) inhibitor (H89) and different cAMP analogues: a PKA‐specific activator (N6‐benzoyl‐adenosine‐cAMP), an exchange protein activated by cAMP‐specific activator (Rp‐8‐chlorophenylthio‐2′‐ O ‐methyl cAMP), and a PKA inhibitor (Rp‐8‐bromo‐cAMP), to elucidate the signalling cascade of cAMP in IL‐17A regulation in T cells. We found that CT induced IL‐17A production and IL‐17A promoter activity in activated CD4 + T cells through a cAMP/PKA pathway. Moreover, this regulation was via cAMP‐response element binding protein (CREB) ‐mediated transcriptional activation by using the transfection of an IL‐17A promoter–luciferase reporter construct and CREB small interfering RNA in Jurkat cells. Also, we showed that CREB bound to the CRE motif located at ?183 of the IL‐17A promoter in?vitro . Most interestingly, not only in CD4 + T cells, CT also enhanced cAMP/PKA‐dependent IL‐17A production and CREB phosphorylation in CD8 + T cells. In conclusion, our data suggest that CT induces an IL‐17A‐dominated immune microenvironment through the cAMP/PKA/CREB signalling pathway. Our study also highlights the potentials of CT and cAMP in modulating T helper type 17 responses in?vivo .
机译：发明内容霍乱毒素（CT）是一种细菌组分，其增加宿主细胞中的细胞内cAMP水平并抑制T细胞活化。最近，据报道，CT诱导T辅助型17-偏斜的树突细胞，并通过营养依赖性途径激活CD4 + T细胞中的白细胞介素-17a（IL-17a）产生。然而，营地调节在T细胞中产生IL-17A产生的潜在机制是完全定义的。在这项研究中，我们利用小分子蛋白激酶A（PKA）抑制剂（H89）和不同的CAMP类似物：PKA特异性活化剂（N6-苯甲酰基 - 腺苷-CAMP），由CAMP特异性活化剂激活的交换蛋白（RP-8-氯苯硫噻嗪-2'- O-甲基CAMP）和PKA抑制剂（RP-8-溴壳），以阐明在T细胞IL-17A调节中的阵营的信号传导级联。我们发现CT通过阵营/ PKA途径诱导活化的CD4 + T细胞中的IL-17A产生和IL-17A启动子活性。此外，通过使用Jurkat细胞中的IL-17A启动子 - 荧光素酶报告器和CREB小干扰RNA的转染，该调节通过CAMP响应元件结合蛋白（CREB）介导的转录活化。此外，我们展示了CREB与IL-17A启动子的183位于β体外的CREB。最有趣的是，不仅在CD4 + T细胞中，CT也增强了CD8 + T细胞中的CAMP / PKA依赖性IL-17A产生和CREB磷酸化。总之，我们的数据表明CT通过CAMP / PKA / CREB信号通路诱导IL-17A主导的免疫微环境。我们的研究还突出了CT和CAMP调制T辅助型17型反应的潜力。

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