Substance P-regulated leukotriene B4 production promotes acute pancreatitis-associated lung injury through neutrophil reverse migration

International Immunopharmacology
Bin LiGuoyong Hu

Abstract

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 grou...Continue Reading

Citations

Sep 21, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Bin LiGuoyong Hu
Apr 2, 2021·Frontiers in Immunology·Jingjing Ji, Jie Fan
Apr 22, 2021·Science Signaling·Monique T FonsecaAlexandre A Steiner
Jun 1, 2021·Frontiers in Cell and Developmental Biology·Gandhi F Pavón-RomeroLuis M Terán

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