Classical Signaling and Trans-Signaling Pathways Stimulated by Megalobrama amblycephala IL-6 and IL-6R.
Classical Signaling and Trans-Signaling Pathways Stimulated by Megalobrama amblycephala IL-6 and IL-6R.
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团头鱼IL-6和IL-6R刺激的经典信号和跨信号通路。
DOI：
10.3390/ijms23042019
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发表时间：
2022-02-11
影响因子：
5.6
通讯作者：
Liu H
中科院分区：
文献类型：
--
作者：
Wang J;Sun Q;Zhang J;Wang H;Liu H
白细胞介素-6（IL-6）是一种多能性细胞因子。IL-6通过经典信号传导（IL-6结合膜IL-6受体/IL-6 R）和反式信号传导（IL-6结合可溶性IL-6 R）在炎症中起双重作用。然而，在硬骨鱼类中，IL-6活性的调节，特别是IL-6反式信号转导介导的信号通路和下游基因的调节，在很大程度上仍不清楚。本研究以草鱼肝细胞（L 8824）、肾细胞（CIK）和原代肝细胞为实验模型。首先，采用定量PCR（qPCR）和western blot检测重组团头鲂IL-6（rmaIL-6）和sIL-6 R（rmasIL-6 R）的生物学活性。Western blot结果显示，rmaIL-6显著上调L 8824细胞和原代肝细胞中的信号转导和转录激活因子3（STAT 3）磷酸化，而rmaIL-6与rmasIL-6 R组合（rmaIL-6+rmasIL-6 R）显著上调所有类型细胞中的STAT 3磷酸化。此外，maIL-6和maIL-6+rmasIL-6 R仅能分别诱导L 8824细胞和CIK细胞的细胞外信号调节激酶1/2（ERK 1/2）磷酸化。因此，IL-6主要通过激活Janus激酶（JAK）/STAT 3途径而不是丝裂原活化蛋白激酶（MEK）/ERK途径起作用。最后，JAK 2/STAT 3通路的激活被证明对于JAK 2/STAT 3通路抑制剂（c188-9和TG 101348）处理后由IL-6反式信号传导诱导的socs 3a和socs 3b的产生是必需的。这些研究结果为了解硬骨鱼类中IL-6的经典信号转导和反式信号转导调控机制提供了功能性的见解，丰富了我们对鱼类免疫学的认识。
Interleukin-6 (IL-6) is a multipotent cytokine. IL-6 plays a dual role in inflammation through both classical signaling (IL-6 binds membrane IL-6 receptor/IL-6R) and trans-signaling (IL-6 binds soluble IL-6R). However, the regulation of IL-6 activity, especially the regulation of signaling pathways and downstream genes mediated by IL-6 trans-signaling, remains largely unclear in teleost. Grass carp (Ctenopharyngodon idellus) hepatic (L8824) cells, kidney (CIK) cells, and primary hepatocytes were used as test models in this study. First, the biological activity of recombinant blunt snout bream (Megalobrama amblycephala) IL-6 (rmaIL-6) and sIL-6R (rmasIL-6R) was verified by quantitative PCR (qPCR) and western blot. The western blot results showed that rmaIL-6 significantly upregulated signal transducer and activator of transcription 3 (STAT3) phosphorylation in L8824 cells and primary hepatocytes, while rmaIL-6 in combination with rmasIL-6R (rmaIL-6+rmasIL-6R) significantly upregulated STAT3 phosphorylation in all types of cells. Furthermore, maIL-6 and maIL-6+rmasIL-6R could only induce extracellular-signal-regulated kinase 1/2 (ERK1/2) phosphorylation in L8824 cells and CIK cells, respectively. Therefore, IL-6 mainly acts by activating the janus kinase (JAK)/STAT3 pathway rather than the mitogen-activated protein kinase (MEK)/ERK pathway. Finally, the activation of the JAK2/STAT3 pathway was shown to be essential for the generation of socs3a and socs3b induced by IL-6 trans-signaling after treatment by JAK2/STAT3 pathway inhibitors (c188-9 and TG101348). These findings provide functional insights into IL-6 classical signaling and trans-signaling regulatory mechanisms in teleost, enriching our knowledge of fish immunology.
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影响因子：
3.6
作者：
Diehl, S;Rincón, M
通讯作者：
Rincón, M
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