National Engineering Research Center of Marine Facilities Aquaculture, Marine Science and Technology College, Zhejiang Ocean University, Zhoushan, 316004, China.
National Engineering Research Center of Marine Facilities Aquaculture, Marine Science and Technology College, Zhejiang Ocean University, Zhoushan, 316004, China.
Fish Shellfish Immunol. 2019 Jan;84:213-222. doi: 10.1016/j.fsi.2018.10.018. Epub 2018 Oct 9.
Interleukin-1 receptor-associated kinase-4 (IRAK4) is considered as the most upstream kinase of IRAKs and plays a vital role in Toll-like receptor/Interleukin-1 receptor (TLR/IL-1R) signal transduction. In the present study, IRAK4 from thick shell mussel Mytilus coruscus (McIRAK4) was identified and characterized. McIRAK4 showed the most similarity to its counterparts in bivalves. The conserved death domain (DD) and catalytic domain of serine/threonine kinases (STKc) were predicted in all examined IRAK4s. McIRAK4 transcripts were constitutively expressed in all examined tissues with the higher expression level in immune related tissues, and were significantly induced in haemocytes upon lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid (poly I:C) challenge. Further, the expression of McIRAK4 was obviously repressed by dsRNA mediated RNA interference (RNAi), meanwhile the proinflammatory cytokines TNF-alpha and IL17 were down-regulated while the antiinflammatory cytokine TGF-β was up-regulated. Additionally, McIRAK4 showed a global cytoplasmic localization in HEK293T cells through fluorescence microscopy. These results collectively indicated that McIRAK4 is one member of IRAK4 subfamily and might play the potential signal transducer role in inflammatory response. The present study provides supplement for TLR-mediated signaling pathway triggered by pathogenic invasions in thick shell mussel, and contributes to the clarification of the innate immune response in molluscs.
白细胞介素-1 受体相关激酶 4（IRAK4）被认为是 IRAKs 中最上游的激酶，在 Toll 样受体/白细胞介素-1 受体（TLR/IL-1R）信号转导中发挥重要作用。在本研究中，从厚壳贻贝 Mytilus coruscus 中鉴定并表征了 IRAK4（McIRAK4）。McIRAK4 与双壳类动物中的对应物最为相似。所有检查的 IRAK4 中都预测到了保守的死亡结构域（DD）和丝氨酸/苏氨酸激酶（STKc）的催化结构域。McIRAK4 转录本在所有检查的组织中持续表达，在免疫相关组织中的表达水平较高，在脂多糖（LPS）和聚肌苷酸-聚胞苷酸（poly I:C）刺激后，在血细胞中显著诱导。此外，dsRNA 介导的 RNA 干扰（RNAi）明显抑制了 McIRAK4 的表达，同时促炎细胞因子 TNF-α和 IL17 下调，抗炎细胞因子 TGF-β上调。此外，通过荧光显微镜观察到 McIRAK4 在 HEK293T 细胞中呈现全细胞质定位。这些结果共同表明，McIRAK4 是 IRAK4 亚家族的一员，可能在炎症反应中发挥潜在的信号转导作用。本研究为厚壳贻贝中病原体入侵引发的 TLR 介导的信号通路提供了补充，有助于阐明软体动物的先天免疫反应。
