Soyasaponin A1 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. (December 2021)

• Record Type: Journal Article
• Authors: Gu, Xiangfu; Tang, Jiaqi; Zhao, Yue; Su, Chuhong; Xiao, Lingyu; Luo, Huiyu; Liu, Yuguo; Xiong, Fei; Zheng, Zhongdaixi; Chen, Junbin; Zha, Longying
• Is Part Of: Journal of functional foods. Volume 87(2021)
• Publication Date: 2021-12
• Subjects: Soyasaponin -- Lipid raft -- Inflammation -- Toll-like receptor 4 -- Cholesterol homeostasis; ABCA1 ATP-binding cassette transporter A1 -- Akt Protein kinase B -- ANOVA Analysis of variance -- ATCC American Type Culture Collection -- BSA Bovine Serum Albumin -- CFP Cyan fluorescent protein -- CO2 Carbon dioxide -- COX-2 Cyclooxygenase 2 -- CTx-B Cholera toxin B subunit -- DAPI 4′, 6-diamidino-2-phenylindole -- DDMP 2, 3-dihydro-2, 5-dihydroxy-6-methyl-4H-pyran-4-one -- DHA Docosahexaenoic acid -- DMEM Dulbecco's modified eagle medium -- ER Endoplasmic reticulum -- FITC Fluorescein isothiocyanate -- FRET Fluorescence resonance energy transfer -- HFD High fat diet -- ICAM-1 Intercellular adhesion molecule 1 -- ICR Institute of cancer research -- IL Interleukin -- iNOS Inducible nitric oxide synthase -- IP Immunoprecipitation -- LPS Lipopolysaccharide -- MAPKs Mitogen-activated protein kinases -- MCP-1 Monocyte chemoattractant protein 1 -- MD2 Myeloid differentiation protein 2 -- MyD88 Myeloid differential protein 88 -- MβCD Methyl β cyclodextrin -- Na2CO3 Sodium carbonate -- NADPH Nicotinamide adenine dinucleotide phosphate -- NF-κB Nuclear factor kappa B -- NO Nitric oxide -- PA Palmitic acid -- PAMPs Pathogen-associated molecular patterns -- PBS Phosphate buffered saline -- PGE2 Prostaglandin E2 -- PI3K Phosphatidylinositol-3-hydroxykinase -- PL Phospholipids -- PMSF Phenylmethylsulfonyl fluoride -- PVDF Polyvinylidene fluoride -- RIPA Radio immunoprecipitation assay -- ROI Region of interest -- ROS Reactive oxygen species -- S1P Site-1 protease -- S2P Site-2 protease -- SCAP SREBP cleavage-activating protein -- SDS-PAGE Sodium dodecyl sulfate polyacrylamide gel electrophoresis -- SFAs Saturated fatty acids -- SREBP2 Sterol regulatory element-binding protein 2 -- SS Soyasaponins -- TBST Tris-buffered saline and tween 20 -- TLR4 Toll-like receptor 4 -- TNF Tumor necrosis factor -- TRIF TIR domain-containing adapter-inducing interferon-β -- YFP Yellow fluorescent protein; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2021.104789
• Languages: English
• ISSNs: 1756-4646

Abstract

Graphical abstract: Highlights: Soyasaponin A1 (SSA1 ) inhibits the lipid rafts-mediated TLR4 signal pathway. SSA1 modify the formation, clustering and size of lipid rafts. Cholesterol replenishment abrogates the anti-inflammatory effects of SSA1 . SSA1 maintains cholesterol homeostasis by binding to it and affecting its metabolism. Abstract: The mechanisms of soyasaponin A1 (SS-A1 ) on antagonizing inflammation via regulating the lipid raft-mediated toll-like receptor 4 (TLR4) signaling are not completely understood. In this study, SS-A1 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-A1 also suppressed the PA-caused dimerization of TLR4 with and its adaptor molecules by applying immunoprecipitation and fluorescence resonance energy transfer. Meanwhile, SS-A1 modified the formation, clustering, and size of lipid rafts and decreased cholesterol in lipid rafts. Cholesterol replenishment abrogated SS-A1 's inhibition on the lipid rafts recruitment and dimerization of TLR4 and its adaptor molecules and its anti-inflammatory activity. Additionally, SS-A1 inhibited the mature sterol regulatory element-binding protein 2 and increases ATP-binding cassette transporter A1. Collectively, SS-A1 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.