Differential expression and potential role of SOCS1 and SOCS3 in Wallerian degeneration in injured peripheral nerve.
Differential expression and potential role of SOCS1 and SOCS3 in Wallerian degeneration in injured peripheral nerve.
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DOI：
10.1016/j.expneurol.2009.06.018
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发表时间：
2010-05
影响因子：
5.3
通讯作者：
David S
中科院分区：
文献类型：
--
作者：
Girolami EI;Bouhy D;Haber M;Johnson H;David S
促炎趋化因子和细胞因子在周围神经损伤后的沃勒变性（WD）中发挥重要作用。这些促炎信号被及时“关闭”，以确保受伤神经的炎症反应受到限制。调节促炎状态关闭的因素尚不完全清楚。细胞因子信号传导（SOCS）蛋白的抑制蛋白是潜在的候选者，可以通过在细胞内水平调节细胞因子信号传导来限制炎症反应。在这项工作中，我们表明，在切割/结扎和挤压损伤后的小鼠坐骨神经中，SOCS1 和 SOCS3 蛋白的表达在 WD 过程中彼此不同。 SOCS1主要由巨噬细胞表达，其表达与JAK2和STAT3信号蛋白的磷酸化以及促炎细胞因子IL-1β和TNFα的表达呈负相关。此外，与挤压损伤相比，切断/结扎的神经表达较低水平的 SOCS1，用 SOCS1 模拟肽治疗会导致损伤后 14 天巨噬细胞数量减少，并在损伤后 1 天减少 IL-1β mRNA 表达。相反，SOCS3的表达主要限于雪旺细胞，并且与IL-6和LIF的表达呈负相关。这些数据表明 SOCS1 和 SOCS3 可能在 WD 中发挥不同的作用，并提供对可能控制受损周围神经炎症和再生的一些潜在调节机制的更好理解。
Pro-inflammatory chemokines and cytokines play an important role in Wallerian degeneration (WD) after peripheral nerve injury. These pro-inflammatory signals are “turned-off” in a timely manner to ensure that the inflammatory response in the injured nerve is limited. The factors that regulate the turning-off of the pro-inflammatory state are not fully understood. The suppressors of cytokine signaling (SOCS) proteins are potential candidates that could limit the inflammatory response by acting to regulate cytokine signaling at the intracellular level. In this work we show that the expression SOCS1 and SOCS3 proteins differ from each other during WD in the mouse sciatic nerve after cut/ligation and crush injuries. SOCS1 is mainly expressed by macrophages and its expression is inversely correlated with phosphorylation of JAK2 and STAT3 signaling proteins and the expression of pro-inflammatory cytokines IL-1β and TNFα. In addition, treatment of cut/ligated nerves, which express lower levels of SOCS1 as compared to crush injury, with a SOCS1 mimetic peptide leads to a decrease in macrophage numbers at 14 days post-injury and reduces IL-1β mRNA expression 1 day post-injury. In contrast, SOCS3 expression is restricted mainly to Schwann cells and is negatively correlated with the expression of IL-6 and LIF. These data suggest that SOCS1 and SOCS3 may play different roles in WD and provide a better understanding of some of the potential regulatory mechanisms that may control inflammation and regeneration in the injured peripheral nerve.
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