Abstract
Acute lung injury (ALI) is a common clinical disease with high morbidity in both humans and animals. Ginsenoside Rg3, a type of traditional Chinese medicine extracted from ginseng, is widely used to cure many inflammation-related diseases. However, the specific molecular mechanism of the effects of ginsenoside Rg3 on inflammation has rarely been reported. Thus, we established a mouse model of lipopolysaccharide (LPS)-induced ALI to investigate the immune protective effects of ginsenoside Rg3 and explore its molecular mechanism. In wild type (WT) mice, we found that ginsenoside Rg3 treatment significantly mitigated pathological damages and reduced myeloperoxidase (MPO) activity as well as the production of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6); furthermore, the production of anti-inflammatory mediators interleukin-10 (IL-10) and transforming growth factor-β (TGF-β), polarization of M2 macrophages and expression levels of the phosphorylation of phosphatidylinositol 3-hydroxy kinase (PI3K), protein kinase B (PKB, also known as AKT), mammalian target of rapamycin (mTOR) and Mer receptor tyrosine kinase (MerTK) were promoted. However, there were no significant differences with regards to the pathological damage, MPO levels, inflammatory cytokine levels, and protein expression levels of the phosphorylation of PI3K, AKT and mTOR between the LPS treatment group and ginsenoside Rg3 group in MerTK-/- mice. Taken together, the present study demonstrated that ginsenoside Rg3 could attenuate LPS-induced ALI by decreasing the levels of pro-inflammatory mediators and increasing the production of anti-inflammatory cytokines. These processes were mediated through MerTK-dependent activation of its downstream the PI3K/AKT/mTOR pathway. These findings identified a new site of the specific anti-inflammatory mechanism of ginsenoside Rg3.
Highlights
MATERIALS AND METHODSAcute lung injury (ALI), is a common clinical disease with a high morbidity rate in both humans and animals, which causes injury to the alveolar epithelial cells and pulmonary capillary endothelial cells because of non-cardiogenic factors, and it can further develop into its severe stage, acute respiratory distress syndrome (ARDS) (Ferguson et al, 2005; Niu et al, 2015; Chen et al, 2017)
In wild type (WT) mice groups, there were no histological changes in the control group, while the group induced by LPS showed significant histological changes characterized by alveolar structure destruction, hemorrhage and inflammatory cell infiltration
These results further proved that ginsenoside Rg3 promotes LPSinduced activation of the phosphatidylinositol 3-hydroxy kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, which is dependent on Mer receptor tyrosine kinase (MerTK)
Summary
MATERIALS AND METHODSAcute lung injury (ALI), is a common clinical disease with a high morbidity rate in both humans and animals, which causes injury to the alveolar epithelial cells and pulmonary capillary endothelial cells because of non-cardiogenic factors, and it can further develop into its severe stage, acute respiratory distress syndrome (ARDS) (Ferguson et al, 2005; Niu et al, 2015; Chen et al, 2017). MerTK is obviously expressed on monocytes, as well as, epithelial and reproductive tissues, and it plays an important role in regulating immune functions such as suppressing the innate immune response and mediating the clearance (efferocytosis) of apoptotic cells (Triantafyllou et al, 2017). It has been reported MerTK that has an inhibitory effect on LPS-induced ALI (Lee et al, 2012a). The phosphatidylinositol 3-hydroxy kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway plays an important role in cell growth, proliferation, apoptosis and autophagy as a crucial intracellular signal transduction pathway (Zhang et al, 2016). It has been demonstrated that the inflammatory response induced by LPS was suppressed by the PI3K/AKT/mTOR pathway (Tsukamoto et al, 2008)
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