DJ-1 Alleviates Neuroinflammation and the Related Blood-Spinal Cord Barrier Destruction by Suppressing NLRP3 Inflammasome Activation via SOCS1/Rac1/ROS Pathway in a Rat Model of Traumatic Spinal Cord Injury

Author:

Cai Lingxin,Gao Liansheng,Zhang Guoqiang,Zeng Hanhai,Wu Xinyan,Tan Xiaoxiao,Qian Cong,Chen Gao

Abstract

DJ-1 has been shown to play essential roles in neuronal protection and anti-inflammation in nervous system diseases. This study aimed to explore how DJ-1 regulates neuroinflammation after traumatic spinal cord injury (t-SCI). The rat model of spinal cord injury was established by the clamping method. The Basso, Beattie, Bresnahan (BBB) score and the inclined plane test (IPT) were used to evaluate neurological function. Western blot was then applied to test the levels of DJ-1, NLRP3, SOCS1, and related proinflammatory factors (cleaved caspase 1, IL-1β and IL-18); ROS level was also examined. The distribution of DJ-1 was assessed by immunofluorescence staining (IF). BSCB integrity was assessed by the level of MMP-9 and tight junction proteins (Claudin-5, Occludin and ZO-1). We found that DJ-1 became significantly elevated after t-SCI and was mainly located in neurons. Knockdown of DJ-1 with specific siRNA aggravated NLRP3 inflammasome-related neuroinflammation and strengthened the disruption of BSCB integrity. However, the upregulation of DJ-1 by Sodium benzoate (SB) reversed these effects and improved neurological function. Furthermore, SOCS1-siRNA attenuated the neuroprotective effects of DJ-1 and increased the ROS, Rac1 and NLRP3. In conclusion, DJ-1 may alleviate neuroinflammation and the related BSCB destruction after t-SCI by suppressing NLRP3 inflammasome activation by SOCS1/Rac1/ROS pathways. DJ-1 shows potential as a feasible target for mediating neuroinflammation after t-SCI.

Funder

National Natural Science Foundation of China

Publisher

MDPI AG

Subject

General Medicine

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