Prevention of LPS-induced lung inflammation by PLAG administration via blocking of IL-6-STAT3-MIP-2 pathway

Abstract Neutrophil plays a key role in the innate immune system through as the first leukocyte to be migrated to the acute inflammatory region. Lung inflammation is an acute respiratory failure and links closely to excessive neutrophil recruitment and severe mortality. The intranasal LPS introduced mice were shown the over-flowed neutrophils into bronchoalveolar. PLAG is a synthetic monoacetyldiacylglycerol (acetyl-DAG). DAG is a lipid second messenger for PKC activator which is associated with an important for cellular functions. The transmigrated neutrophils in alveolar by LPS stimulation were completely blocked by PLAG administration. LPS-induced cell migration associated factors such as IL-6, MIP-2 and S100A8/9 were decreased by addition of PLAG. STAT3 phosphorylation which related to neutrophil migration was significantly down regulated in PLAG dieted mice. Interestingly, the selectivity of PLAG in the ameliorating of excessive neutrophil migration was verified when compared with PLAG analogues and metabolites. Post treatment of PLAG has also therapeutic effect on LPS-induced lung inflammation. These data could be utilized as a most potential therapeutic agent for lung inflammation through regulation of neutrophil transmigration via blocking of IL-6-STAT3-MIP-2 pathway.