1. Academic Validation
  2. Tuftsin ameliorates splenic inflammatory injury by promoting neuropilin-1 in severe acute pancreatitis

Tuftsin ameliorates splenic inflammatory injury by promoting neuropilin-1 in severe acute pancreatitis

  • Biochem Pharmacol. 2022 May;199:115030. doi: 10.1016/j.bcp.2022.115030.
E Wen 1 Guang Xin 1 Shiyi Li 1 Yuman Dong 1 Yuda Zhu 1 Chengyu Wan 1 Xiuxian Yu 1 Zeliang Wei 1 Yilan Wang 1 Fan Li 1 Kun Zhang 1 Hai Niu 1 Wen Huang 2
Affiliations

Affiliations

  • 1 Laboratory of Ethnopharmacology, Tissue-orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • 2 Laboratory of Ethnopharmacology, Tissue-orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China. Electronic address: huangwen@scu.edu.cn.
Abstract

Severe acute pancreatitis (SAP)-associated spleen injury causing immune disturbances aggravates organs injuries, which contributes to higher mortality rate. However, there are no effective drugs to cure SAP-induced spleen injury. Here, we found that Tuftsin (TN) is effective for ameliorating SAP-induced pathological damage and inflammation of spleen, mainly via alleviating mitochondrial dysfunction, oxidative stress, ATP depletion and the expression of pro-inflammatory factors. We further found that TN promoted anti-inflammatory macrophage phenotype M2 via up-regulating NRP1 on macrophage in spleen during SAP. Meanwhile, EG00229 (an inhibitor of NRP1 bound to TN) weakened TN's therapeutic effect in SAP-associated spleen injury. And EG00229 also inhibited M2 macrophage, leading to increasing inflammasome formation. Additionally, EG00229 reduced the protective efficiency of TN on mitochondrial dysfunction, and inflammation injury via NRP1 in spleen caused by SAP. Similarly, siRNA-Nrp1 into macrophage also prevented TN's inhibition on Apoptosis. These findings reveal that TN alleviates SAP-induced spleen injury by promoting NRP1.

Keywords

Inflammation; Macrophage; NRP1; Severe acute pancreatitis; Spleen injury; Tuftsin.

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