Silencing ApoC3 alleviates LPS-induced acute lung injury by inhibiting TLR signaling pathway

This study aims to confirm whether apolipoprotein C3 (ApoC3) can regulate the inflammatory response and tissue damage in acute lung injury (ALI) and explore its regulatory pathway. ALI mouse model was established by intraperitoneal injection of lipopolysaccharide (LPS). ApoC3 levels were detected by real-time quantitative polymerase chain reaction, immunohistochemistry, and western blot assays. The levels of various inflammatory factors were detected by enzyme-linked immunosorbent assay and western blot analysis. Finally, the expression of toll-like receptor (TLR)/nuclear factor kappa B (NF-κB) signaling pathway-related protein [TLR2, myeloid differentiation primary response protein 88 (MyD88), IL-1 receptor-associated kinase 1 (IRAK1), NF-κB p65, and inhibitor of kappa B alpha (IκBα)], SLP adaptor and CSK interacting membrane protein (SCIMP), spleen tyrosine kinase (Syk), and phosphorylated (p)-Syk was detected by western blot analysis. ApoC3 was overexpressed in ALI mouse lung tissue and cell inflammation model. Silencing ApoC3 reduced inflammatory factors and alleviated lung tissue damage in ALI mice. Silencing ApoC3 reduced inflammatory factors and downregulated the expression of TLR2, MyD88, IRAK1, NF-κB p65, and increased IκBα expression in LPS-treated RAW264.7 cells. Moreover, co-transfection of si-TLR2 and shApoC3 further enhanced the inhibitory effects on the levels of inflammatory factors induced by silencing ApoC3. ApoC3 overexpression increased the levels of inflammatory factors and protein expression of SCIMP and p-Syk, while silencing TLR2 reversed the promotive effects of ApoC3 overexpression on above factors. In LPS-induced ALI mouse model and inflammatory cell model, downregulation of ApoC3 reduced inflammatory factors and relieved tissue damage. This process might be achieved through the TLR pathway.