Emergency Intensive Care Unit, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Front Immunol. 2024 May 17;15:1405622. doi: 10.3389/fimmu.2024.1405622. eCollection 2024.
Severe acute pancreatitis (SAP) is an inflammatory disorder affecting the gastrointestinal system. Intestinal injury plays an important role in the treatment of severe acute pancreatitis. In this study, we mainly investigated the role of S1PR2 in regulating macrophage pyroptosis in the intestinal injury of severe acute pancreatitis.
The SAP model was constructed using cerulein and lipopolysaccharide, and the expression of S1PR2 was inhibited by JTE-013 to detect the degree of pancreatitis and intestinal tissue damage in mice. Meanwhile, the level of pyroptosis-related protein was detected by western blot, the level of related mRNA was detected by PCR, and the level of serum inflammatory factors was detected by ELISA. experiments, LPS+ATP was used to construct the pyroptosis model of THP-1. After knockdown and overexpression of S1PR2, the pyroptosis proteins level was detected by western blot, the related mRNA level was detected by PCR, and the level of cell supernatant inflammatory factors were detected by ELISA. A rescue experiment was used to verify the sufficient necessity of the RhoA/ROCK pathway in S1PR2-induced pyroptosis. Meanwhile, THP-1 and FHC were co-cultured to verify that cytokines released by THP-1 after damage could regulate FHC damage.
Our results demonstrated that JTE-013 effectively attenuated intestinal injury and inflammation in mice with SAP. Furthermore, we observed a significant reduction in the expression of pyroptosis-related proteins within the intestinal tissue of SAP mice upon treatment with JTE-013. We confirmed the involvement of S1PR2 in THP-1 cell pyroptosis . Specifically, activation of S1PR2 triggered pyroptosis in THP-1 cells through the RhoA/ROCK signaling pathway. Moreover, it was observed that inflammatory factors released during THP-1 cell pyroptosis exerted an impact on cohesin expression in FHC cells.
The involvement of S1PR2 in SAP-induced intestinal mucosal injury may be attributed to its regulation of macrophage pyroptosis.
重症急性胰腺炎（SAP）是一种影响胃肠道系统的炎症性疾病。肠道损伤在重症急性胰腺炎的治疗中起着重要作用。在这项研究中，我们主要研究了 S1PR2 在调节重症急性胰腺炎肠道损伤中巨噬细胞细胞焦亡中的作用。
使用 Cerulein 和脂多糖构建 SAP 模型，并用 JTE-013 抑制 S1PR2 的表达，以检测小鼠胰腺炎和肠道组织损伤的程度。同时，通过 Western blot 检测细胞焦亡相关蛋白的水平，PCR 检测相关 mRNA 的水平，ELISA 检测血清炎症因子的水平。在体外实验中，用 LPS+ATP 构建 THP-1 细胞的细胞焦亡模型。用 S1PR2 的敲低和过表达后，通过 Western blot 检测细胞焦亡蛋白的水平，PCR 检测相关 mRNA 的水平，ELISA 检测细胞上清炎症因子的水平。用 rescue 实验验证 S1PR2 诱导的细胞焦亡中 RhoA/ROCK 通路的充分必要性。同时，THP-1 和 FHC 共培养，验证受损的 THP-1 释放的细胞因子可以调节 FHC 的损伤。
我们的结果表明，JTE-013 可有效减轻 SAP 小鼠的肠道损伤和炎症。此外，我们观察到 JTE-013 处理后 SAP 小鼠肠道组织中细胞焦亡相关蛋白的表达显著减少。我们证实了 S1PR2 在 THP-1 细胞细胞焦亡中的作用。具体来说，S1PR2 的激活通过 RhoA/ROCK 信号通路触发 THP-1 细胞的细胞焦亡。此外，还观察到 THP-1 细胞细胞焦亡过程中释放的炎症因子对 FHC 细胞黏着蛋白的表达产生影响。
S1PR2 参与 SAP 诱导的肠道黏膜损伤可能与其调节巨噬细胞细胞焦亡有关。
