Reduction of Silent Information Regulator 1 Activates Interleukin-33/ST2 Signaling and Contributes to Neuropathic Pain Induced by Spared Nerve Injury in Rats
Yanyan Zeng, Yu Shi, Hongrui Zhan, Wei Liu, Guiyuan Cai, Haili Zhong, Yaping Wang, Shangjie Chen, Shimin Huang, Wen Wu
Abstract
Emerging studies demonstrated that IL-33 and its receptor ST2 acted as a key factor in inflammatory disease. Besides, accumulating evidences evaluated that the cytokines TNF-α and IL-1β could trigger inflammatory cascade. Importantly, SIRT1 were validated to suppress the expression of inflammatory cytokines. However, whether the effects of SIRT1 on IL-33/ST2 signaling and IL-33 initiates the inflammatory cascade via modulating the TNF-α and IL-1β remain unclear. In the present study, we found that the DRG IL-33 and ST2 upregulated in SNI rats and intrathecal injection of either IL-33 antibody or ST2 antibody alleviated the mechanical allodynia and downregulated TNF-α and IL-1β induced by SNI. In addition, activation of SIRT1 decreased the enhanced DRG IL-33/ST2 signaling in SNI rats. Artificial inactivation of SIRT1 via intrathecal injection of SIRT1 antagonist could induce mechanical allodynia and upregulate of IL-33 and ST2. These results demonstrated that reduction of SIRT1 could induce upregulation of DRG IL-33 and ST2 and contribute to mechanical allodynia induced by SNI in rats.