State Key Laboratory of Freshwater Ecology and Biotechnology, and Key Laboratory of Aquaculture Disease Control, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei Province, 430072, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
State Key Laboratory of Freshwater Ecology and Biotechnology, and Key Laboratory of Aquaculture Disease Control, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei Province, 430072, China.
Dev Comp Immunol. 2019 Aug;97:64-75. doi: 10.1016/j.dci.2019.03.017. Epub 2019 Mar 29.
Interleukin (IL)-10 is an immune-regulatory cytokine with multiple functions. In the current study, IL-10 and its two receptors, IL-10R1 and IL-10R2 were identified in mandarin fish, Siniperca chuatsi. The inhibitory effect of mandarin fish IL-10 was investigated on pro-inflammatory cytokine expression and the ligand-receptor relationship. This IL-10 possesses conserved cysteine residues, predicted α-helices and a typical IL-10 family signature motif, similar to its mammalian orthologue, and IL-10R1 harbours predicted JAK1 and STAT3 binding sites in the intracellular region. The fish IL-10 and IL-10R1 exhibit high expression levels in several immune-related organs/tissues, such as spleen, trunk kidney and head kidney, and IL-10R2 possesses a constitutive expression pattern. The expression of IL-10 shows significant increase in spleen from infectious spleen and kidney necrosis virus (ISKNV) infected mandarin fish, where the two receptors also exhibit different levels of induced expression. Mandarin fish IL-10 also exhibits significant response to the stimulation of LPS, PHA and PMA, with the two receptors exhibiting an interesting decrease in expression following the treatment of PMA. The pro-inflammatory cytokines, IL-6, IL-1β, IL-8, TNF-α, show diminished up-regulation in LPS-stimulated splenocytes pre-incubated with IL-10, indicating the anti-inflammatory roles of mandarin fish IL-10. In EPC cells transfected with different combinations of receptors, IL-10 can enhance the expression of suppressor of cytokine signalling 3 (SOCS3) only when IL-10R1 and IL-10R2 are both expressed, suggesting the participation of the two receptors in signal transduction of mandarin fish IL-10. Similar results are observed with the usage of chimeric receptors, IL-10R1/CRFB1 and IL-10R2/CRFB5. Overall, mandarin fish IL-10 shares conserved ligand-receptor system and the prototypical inhibitory activities on pro-inflammatory cytokine expression with mammalian IL-10, implying the evolutionary conservation of this cytokine.
白细胞介素 (IL)-10 是一种具有多种功能的免疫调节细胞因子。在本研究中，鉴定了鳜鱼 Siniperca chuatsi 的 IL-10 及其两种受体，IL-10R1 和 IL-10R2。研究了鳜鱼 IL-10 对促炎细胞因子表达的抑制作用及其配体-受体关系。这种 IL-10 具有保守的半胱氨酸残基、预测的α-螺旋和典型的 IL-10 家族特征基序，与哺乳动物的同源物相似，而 IL-10R1 在细胞内区域具有预测的 JAK1 和 STAT3 结合位点。鱼 IL-10 和 IL-10R1 在几种免疫相关的器官/组织中表现出高表达水平，如脾脏、躯干肾脏和头部肾脏，而 IL-10R2 则表现出组成型表达模式。IL-10 的表达在传染性脾脏和肾脏坏死病毒 (ISKNV) 感染的鳜鱼脾脏中显著增加，两种受体也表现出不同水平的诱导表达。鳜鱼 IL-10 也对 LPS、PHA 和 PMA 的刺激表现出显著的反应，在用 PMA 处理后，两种受体的表达呈有趣的下降趋势。在预先用 IL-10 孵育的 LPS 刺激的脾细胞中，促炎细胞因子 IL-6、IL-1β、IL-8、TNF-α 的上调受到抑制，表明鳜鱼 IL-10 具有抗炎作用。在转染不同受体组合的 EPC 细胞中，只有当同时表达 IL-10R1 和 IL-10R2 时，IL-10 才能增强细胞因子信号转导抑制因子 3 (SOCS3) 的表达，表明这两种受体参与了鳜鱼 IL-10 的信号转导。使用嵌合受体 IL-10R1/CRFB1 和 IL-10R2/CRFB5 也观察到类似的结果。总体而言，鳜鱼 IL-10 与哺乳动物 IL-10 具有保守的配体-受体系统和对促炎细胞因子表达的典型抑制活性，表明这种细胞因子在进化上是保守的。
