白三烯B4
MAPK/ERK通路
激酶
药理学
蛋白激酶C
急性胰腺炎
脂多糖
医学
化学
炎症
免疫学
内科学
生物化学
作者
Bin Li,Xiao Han,Xin Ye,Jiahua Ni,Jianghong Wu,Jing Dai,Zengkai Wu,Congying Chen,Rong Wan,Xingpeng Wang,Guoyong Hu
标识
DOI:10.1016/j.intimp.2018.02.017
摘要
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 (rTEM) into the circulation and alleviated the severity of ALI. In vitro, treatment of pancreatic acinar cells with SP increased LTB4 production. Furthermore, SP treatment increased phosphorylation of protein kinase C (PKC) α 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 PKCα/MAPK pathway, which further promotes AP-associated ALI through neutrophil rTEM.
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