Center for Informational Biology, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China.
Center for Informational Biology, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China.
Gene. 2020 May 30;741:144579. doi: 10.1016/j.gene.2020.144579. Epub 2020 Mar 17.
Interleukin (IL)-10 is a critical anti-inflammatory and late cytokine being produced after the proinflammatory mediators while IL-6 is a promptly synthesized cytokine in response to inflammation in mammals. This chronological expression of interleukin (Il)-6 and Il-10 was also found in grass carp head kidney leucocytes (HKLs) treated by heat-killed Aeromonas hydrophila, supporting the possible interplay between grass carp (gc)Il-6 and gcIl-10 in HKLs. Our further findings were in agreement with this hypothesis that recombinant gcIl-6 (rgcIl-6) promptly and transiently increased gcil10 mRNA levels in grass carp HKLs. Moreover, rgcIl-6 enhanced its own mRNA level and this self-enhancement of gcil6 mRNA level could be partially blocked by rgcIl-10. These results collectively suggest that gcIl-10 production stimulated by gcIl-6 may provide a negative feedback to gcIl-6 production. Interestingly, rgcIl-6 significantly decreased gcil10 mRNA levels in grass carp HKLs after the treatment for 12 and 24 h in contrast to its enhancement of gcil10 levels after the treatment for 3 h. Involvement of Stat3 but not MEK, p38 MAPK or JNK pathway in the increase of gcil10 mRNA levels by rgcIl-6 was revealed by using the signaling pathway inhibitors. This was supported by the fact that rgcIl-6 stimulated Stat3 phosphorylation in grass carp HKLs. Furthermore, rgcIl-6 had no effect on the stability of gcil10 mRNA after the treatment for 3 to 36 h while it increased gcil10 promoter activity after the treatment for 24 h. Taken these data together, gcIl-6 can stimulate Il-10 production at early stage but subsequently inhibit il10 mRNA expression in grass carp HKLs, shedding light on the dynamic regulation of il10 mRNA expression by Il-6 in fish immune cells.
白细胞介素（IL）-10 是一种关键的抗炎和晚期细胞因子，在促炎介质产生后产生，而 IL-6 是哺乳动物中对炎症迅速合成的细胞因子。在受嗜水气单胞菌热灭活处理的草鱼头肾白细胞（HKL）中也发现了白细胞介素（Il）-6 和 Il-10 的这种时间表达，支持草鱼（gc）Il-6 和 gcIl-10 在 HKL 中可能存在相互作用。我们的进一步发现与这一假设一致，即重组 gcIl-6（rgcIl-6）在草鱼 HKL 中迅速且短暂地增加了 gcil10 mRNA 水平。此外，rgcIl-6 增强了自身的 mRNA 水平，而这种 rgcIl-6 mRNA 水平的自我增强可以部分被 rgcIl-10 阻断。这些结果共同表明，gcIl-10 的产生受 gcIl-6 刺激可能为 gcIl-6 的产生提供负反馈。有趣的是，rgcIl-6 在处理 3 小时后显著降低了草鱼 HKL 中的 gcil10 mRNA 水平，但在处理 12 和 24 小时后降低了 gcil10 水平。通过使用信号通路抑制剂揭示了 rgcIl-6 增加 gcil10 mRNA 水平涉及 Stat3 而不是 MEK、p38 MAPK 或 JNK 通路。这一事实得到了 rgcIl-6 刺激草鱼 HKL 中 Stat3 磷酸化的支持。此外，rgcIl-6 在处理 3 至 36 小时后对 gcil10 mRNA 的稳定性没有影响，但在处理 24 小时后增加了 gcil10 启动子活性。综合这些数据，gcIl-6 可以在早期刺激 Il-10 的产生，但随后抑制草鱼 HKL 中 il10 mRNA 的表达，这为鱼类免疫细胞中 Il-6 对 il10 mRNA 表达的动态调控提供了线索。
