Soyasaponin Al inhibits the lipid raft recruitment and dimerization of TLR4, MyD88, and TRIF by maintaining cholesterol homeostasis in palmitic acid-stimulated inflammatory Raw264.7 macrophage cell line

The mechanisms of soyasaponin A(1) (SS-A(1)) on antagonizing inflammation via regulating the lipid raft-mediated toll-like receptor 4 (TLR4) signaling are not completely understood. In this study, SS-A(1) inhibited palmitic acid (PA)-induced recruitments of TLR4 and its adaptor molecules into lipid rafts in Raw264.7 macrophage cell line by using ultracentrifugation and confocal microscopy. SS-A(1) also suppressed the PA-caused dimerization of TLR4 with and its adaptor molecules by applying immunoprecipitation and fluorescence resonance energy transfer. Meanwhile, SS-A(1) modified the formation, clustering, and size of lipid rafts and decreased cholesterol in lipid rafts. Cholesterol replenishment abrogated SS-A(1) 's inhibition on the lipid rafts recruitment and dimerization of TLR4 and its adaptor molecules and its anti-inflammatory activity. Additionally, SS-A(1) inhibited the mature sterol regulatory element-binding protein 2 and increases ATP-binding cassette transporter Al. Collectively, SS-A(1) inhibits the lipid raft recruitment and dimerization of TLR4 and its adaptor molecules by maintaining cholesterol homeostasis in PA-stimulated inflammatory Raw264.7 macrophage cell line.

Automated summary

The study shows that SS-A(1) inhibits inflammation by regulating the lipid raft-mediated TLR4 signaling, affecting the recruitment and dimerization of TLR4 by maintaining cholesterol homeostasis.