Abstract：
Neuroinflammation and microglia polarization play pivotal roles in brain injury induced by intracerebral hemorrhage (ICH). Despite the well-established involvement of CXC motif chemokine ligand 16 (CXCL16) in regulating inflammatory responses across various diseases, its specific functions in the context of neuroinflammation and microglial polarization following ICH remain elusive. In this study, we investigated the impact of CXCL16 on neuroinflammation and microglia polarization using both mouse and cell models. Our findings revealed elevated CXCL16 expression in mice following ICH and in BV2 cells after lipopolysaccharide (LPS) stimulation. Specific silencing of CXCL16 using siRNA led to a reduction in the expression of neuroinflammatory factors, including IL-1β and IL-6, as well as decreased expression of the M1 microglia marker iNOS. Simultaneously, it enhanced the expression of anti-inflammatory factors such as IL-10 and the M2 microglia marker Arg-1. These results were consistent across both mouse and cell models. Intriguingly, co-administration of the PI3K-specific agonist 740 Y-P with siRNA in LPS-stimulated cells reversed the effects of siRNA. In conclusion, silencing CXCL16 can positively alleviate neuroinflammation and M1 microglial polarization in BV2 inflammation models and ICH mice. Furthermore, in BV2 cells, this beneficial effect is mediated through the PI3K/Akt pathway. Inhibition of CXCL16 could be a novel approach for treating and diagnosing cerebral hemorrhage.
摘要：
神经炎症和小胶质细胞极化在脑出血（ICH）引起的脑损伤中起关键作用。尽管CXC基序趋化因子配体16（CXCL16）在调节各种疾病的炎症反应中已得到证实，其在ICH后神经炎症和小胶质细胞极化背景下的特定功能仍然难以捉摸.在这项研究中,我们使用小鼠和细胞模型研究了CXCL16对神经炎症和小胶质细胞极化的影响.我们的发现表明，在ICH后小鼠和脂多糖（LPS）刺激后BV2细胞中CXCL16的表达升高。使用siRNA特异性沉默CXCL16导致神经炎症因子的表达减少,包括IL-1β和IL-6，以及M1小胶质细胞标志物iNOS的表达降低。同时,它增强了抗炎因子如IL-10和M2小胶质细胞标志物Arg-1的表达。这些结果在小鼠和细胞模型中都是一致的。有趣的是，在LPS刺激的细胞中共同施用PI3K特异性激动剂740Y-P与siRNA逆转了siRNA的作用。总之,沉默CXCL16可显著减轻BV2炎症模型和ICH小鼠的神经炎症和M1小胶质细胞极化。此外，在BV2细胞中，这种有益作用是通过PI3K/Akt途径介导的。抑制CXCL16可能是治疗和诊断脑出血的新方法。
