Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, 7 Nanhai Road, Qingdao 266071, PR China.
Dev Comp Immunol. 2011 Feb;35(2):174-81. doi: 10.1016/j.dci.2010.09.006. Epub 2010 Sep 30.
Proteins of the suppressor of cytokine signaling (SOCS) family function as inducible feedback inhibitors of cytokine signaling via the JAK/STAT pathway. Although several SOCS isoforms have been identified in teleosts, their immunological functions remain largely unknown. In this study, we identified in turbot Scophthalmus maximus a SOCS homologue (named SmSOCS3) of the mammalian SOCS3 type. The deduced amino acid sequence of SmSOCS3 contains 205 residues and shares extensive overall identities (60-82%) with those of known fish SOCS3. In silico analyses revealed that, like typical SOCS3, SmSOCS3 possesses a kinase inhibitor region (KIR), a Src homology 2 (SH2) domain, and a SOCS box domain. Under physiological conditions SmSOCS3 expression was detected, in increasing order, in blood, brain, heart, kidney, liver, spleen, muscle, and gill. Experimental infection of turbot with a bacterial pathogen induced significant SmSOCS3 expression in kidney, spleen, liver, and gill in time-dependent manners. Examination of SmSOCS3 expression in head kidney (HK) macrophages showed that SmSOCS3 transcription was significantly upregulated in the presence of purified recombinant TNF-α. On the other hand, SmSOCS3 overexpression in HK macrophages inhibited the transcription of TNF-α as well as IL-1β and CC-chemokine. In addition, SmSOCS3 overexpression significantly reduced macrophage respiratory burst activity, nitric oxide production, and bactericidal activity. Taken together, these results suggest that SmSOCS3 is a cytokine-inducible suppressor of pro-inflammatory cytokine signaling in HK macrophages and that regulated expression of SmSOCS3 is required for optimal innate immune response against bacterial infection.
抑制细胞因子信号（SOCS）家族的蛋白通过 JAK/STAT 途径作为细胞因子信号的诱导反馈抑制剂。尽管在硬骨鱼类中已经鉴定出几种 SOCS 同工型，但它们的免疫学功能在很大程度上仍然未知。在这项研究中，我们在大菱鲆 Scophthalmus maximus 中鉴定了一种哺乳动物 SOCS3 型的 SOCS 同源物（命名为 SmSOCS3）。SmSOCS3 的推断氨基酸序列包含 205 个残基，与已知鱼类 SOCS3 具有广泛的整体同一性（60-82%）。计算机分析表明，与典型的 SOCS3 一样，SmSOCS3 具有激酶抑制区（KIR）、Src 同源 2（SH2）结构域和 SOCS 盒结构域。在生理条件下，SmSOCS3 在血液、大脑、心脏、肾脏、肝脏、脾脏、肌肉和鳃中依次被检测到。实验感染细菌病原体后，SmSOCS3 在肾脏、脾脏、肝脏和鳃中的表达呈时间依赖性增加。在头肾（HK）巨噬细胞中检查 SmSOCS3 的表达，发现 SmSOCS3 转录在存在纯化的重组 TNF-α时显著上调。另一方面，HK 巨噬细胞中 SmSOCS3 的过表达抑制了 TNF-α以及 IL-1β和 CC 趋化因子的转录。此外，SmSOCS3 的过表达显著降低了巨噬细胞呼吸爆发活性、一氧化氮产生和杀菌活性。综上所述，这些结果表明 SmSOCS3 是 HK 巨噬细胞中细胞因子诱导的促炎细胞因子信号的抑制剂，SmSOCS3 的调节表达是对细菌感染的最佳固有免疫反应所必需的。
