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1‐palmitoyl‐2‐linoleoyl‐3‐acetyl‐rac‐glycerol (PLAG) reduces hepatic injury in concanavalin A‐treated mice
Author(s) -
Ko Young E.,
Yoon Sun Y.,
Ly Sun Y.,
Kim Joo H.,
Sohn Ki Y.,
Kim Jae W.
Publication year - 2018
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.26299
Subject(s) - concanavalin a , biology , hepatocyte , endocrinology , cytokine , liver injury , medicine , stat protein , inflammation , immunology , signal transduction , in vitro , stat3 , microbiology and biotechnology , biochemistry
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.