1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) reduces hepatic injury in concanavalin A-treated mice

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Title
1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) reduces hepatic injury in concanavalin A-treated mice
Author(s)
Young Eun Ko; S Y Yoon; S Y Ly; J H Kim; K Y Sohn; Jae Wha Kim
Bibliographic Citation
Journal of Cellular Biochemistry, vol. 119, no. 2, pp. 1392-1405
Publication Year
2018
Abstract
1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG), a chemically synthesized monoacetyldiaglyceride, is one of the constituents in Sika deer antlers and has been known traditionally as having immunomodulatory effects. However, the mechanism by which PLAG controls neutrophil migration, which evokes liver injury in the hepatitis animal model, remains largely unknown. This study was designed to evaluate the immunomodulatory effects of PLAG on cytokine secretion and neutrophil migration in vivo and in vitro. Concanavalin A (Con A) induced leukocyte infiltration in the liver and increased plasma cytokine levels. Pretreatment with PLAG reduced the levels of interleukin (IL)-4, IL-6, IL-10, and CXCL2, but maintained interferon (IFN)-γ levels and modulated neutrophil recruitment toward the liver. Furthermore, the mRNA and protein levels of IL-4 and CXCL2 in liver tissue were also decreased in the Con A-treated mice. Liver histology analyses showed that PLAG reduced Con A-induced hepatic necrosis, which was accompanied by leukocyte infiltration. The in vitro studies revealed that PLAG reduced IL-4 secretion in Con A stimulated T cell and blocked signal transducer and activator of transcription 6 (STAT6) Con A induced hepatocyte. PLAG attenuated IL-4 induced activation of atypical protein kinase C (PKC)/STAT6 in hepatocytes and inhibited neutrophil migration toward the liver tissue through suppression of IL-8/vascular cell adhesion molecule (VCAM) expression. These results suggest that PLAG could mitigate excess neutrophil migration into liver tissue and potentially have a therapeutic effect on immune-mediated liver injury. ⓒ 2017 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc.
Keyword
atypical PKCconcanavalin A-induced hepatitisneutrophilPLAGSTAT6
ISSN
0730-2312
Publisher
Wiley
DOI
http://dx.doi.org/10.1002/jcb.26299
Type
Article
Appears in Collections:
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
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