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TLR2 inhibition ameliorates the amplification effect of LPS on lipid accumulation and lipotoxicity in hepatic cells

Year: 2021

Type: article

Abstract: BACKGROUND: -derived lipopolysaccharide (LPS) on lipid accumulation and lipotoxicity in palmitic acid (PA)-treated L02 cell as an NAFLD cell model, and the role of TLR2 in this process. METHODS: Oil red O staining assay and free fatty acid (FFA) content test were performed to determine the effects of LPS on lipid accumulation in a PA-induced NAFLD cell model with or without TLR2 inhibition. The levels of IL-6 and TNF-α were measured to investigate inflammation conditions. Hoechst 33342 staining assay and Caspase-3 activity assay were used to test cell apoptosis, and the expression levels of proteins in the IRS1/PI3K/AKT signaling pathway, TLR2/MyD88/IKKα/NF-κB signaling pathway, and mitochondrion-dependent apoptotic signaling pathway were detected using Western blot. RESULTS: Lipid accumulation, pro-inflammatory cytokine release, and cell apoptosis with high levels were observed in the PA-induced NAFLD cell model, and LPS aggravated these processes. Whereas TLR2 inhibition could significantly ameliorate PA-induced and LPS-amplified lipid accumulation, inflammatory, and cell apoptosis, it had no significant effect on L02 cells treated with LPS alone. CONCLUSIONS: These results were confirmed by activation or inhibition of the IRS1/PI3K/AKT signaling pathway, TLR2/MyD88/IKKα/NF-κB signaling pathway, and mitochondrion-dependent apoptotic signaling pathway, and were reflected by changes on their proteins expression. TLR2 is involved in PA-induced lipid accumulation and lipotoxicity in L02 cells, which could be aggravated by LPS, although LPS-induced amplification might not be through direct interaction with TLR2.

Source: Annals of Translational Medicine

DOI: 10.21037/atm-21-4012