期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 57, 期 -, 页码 147-156出版社
ELSEVIER
DOI: 10.1016/j.intimp.2018.02.017
关键词
Acute pancreatitis; Acute lung injury; Leukotriene B4; Substance P; Reverse transendothelial cell migration
资金
- National Natural Science Foundation of China [81370568, 81670584, 81570580, 81400663, 81372643]
- Doctoral Innovation Fund of Shanghai Jiao Tong University School of Medicine [BXJ201735]
Leukotriene B4 (LTB4) is a potent chemoattractant and inflammatory mediator involved in multiple inflammatory diseases. Substance P (SP) has been reported to promote production of LTB4 in itch-associated response in vivo and in some immune cells in vitro. Here, we investigated the role of LTB4 in acute pancreatitis (AP), AP-associated acute lung injury (ALI) and the related mechanisms of LTB4 production in AP. In vivo, murine AP model was induced by caerulein and lipopolysaccharide or L-arginine. The levels of LTB4 and its specific receptor BLT1 were markedly upregulated in both AP models. Blockade of BLT1 by LY293111 attenuated the severity of AP, decreased neutrophil reverse transendothelial cell migration (ITEM) into the circulation and alleviated the severity of ALL In vitro, treatment of pancreatic acinar cells with SP increased LTB4 production. Furthermore, SP treatment increased phosphorylation of protein kinase C (PKC) a and mitogen activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), p-38 MAPK and c-Jun NH2-terminal kinase (JNK). Finally, blockade of neurokinin-1 receptor by CP96345 significantly attenuated the severity of AP and decreased the level of LTB4 when compared to AP group. In summary, these results show that SP regulates the production of LTB4 via PKC alpha/MAPK pathway, which further promotes AP-associated ALI through neutrophil rTEM.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据