Soy protein inhibits inflammation-induced VCAM-1 and inflammatory cytokine induction by inhibiting the NF-κB and AKT signaling pathway in apolipoprotein E–deficient mice

• Published in: European journal of nutrition Vol. 53; no. 1; pp. 135 - 148
• Main Authors: Burris, Ramona L., Ng, Hang-Pong, Nagarajan, Shanmugam
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.02.2014; Springer
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Aorta - drug effects; Aorta - metabolism; Apolipoproteins E - genetics; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Caseins - administration & dosage; Cell Adhesion - drug effects; Chemistry; Chemistry and Materials Science; Cytokines - metabolism; Disorders of blood lipids. Hyperlipoproteinemia; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Human Umbilical Vein Endothelial Cells; Humans; Inflammation - drug therapy; Lipopolysaccharides - adverse effects; Medical sciences; Metabolic diseases; Mice; Mice, Inbred C57BL; Mice, Knockout; NF-kappa B - antagonists & inhibitors; NF-kappa B - genetics; NF-kappa B - metabolism; Nutrition; Original Contribution; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction; Soybean Proteins - pharmacology; Vascular Cell Adhesion Molecule-1 - genetics; Vascular Cell Adhesion Molecule-1 - metabolism; Vertebrates: anatomy and physiology, studies on body, several organs or systems; VCAM-1; Inflammation; Hyperlipidemia; Soy peptides; Atherosclerosis; Peptides; Cardiovascular disease; Lipids; Soybean; Vascular disease; Signal transduction; Apolipoprotein E; Hyperlipemia; Dyslipemia; Nutrition; Induction; Rodentia; Cytokine; Metabolic diseases; Soy protein; Grain legume; Vertebrata; Mammalia; Mouse; Animal
• ISSN: 1436-6207; 1436-6215
• DOI: 10.1007/s00394-013-0509-7

Purpose Inflammation is a hallmark of many diseases, such as atherosclerosis, autoimmune diseases, obesity, and cancer. Isoflavone-free soy protein diet (SPI − ) has been shown to reduce atherosclerotic lesions in a hyperlipidemic mouse model compared to casein (CAS)-fed mice, despite unchanged serum lipid levels. However, possible mechanisms contributing to the athero-protective effect of soy protein remain unknown. Therefore, we investigated whether and how SPI − diet inhibits inflammatory responses associated with atherosclerosis. Methods Apolipoprotein E knockout (apoE−/−) mice (5-week) were fed CAS or SPI − diet for 1 or 5 week to determine LPS- and hyperlipidemia-induced acute and chronic inflammatory responses, respectively. Expression of NF-κB-dependent inflammation mediators such as VCAM-1, TNF-α, and MCP-1 were determined in aorta and liver. NF-κB, MAP kinase, and AKT activation was determined to address mechanisms contributing to the anti-inflammatory properties of soy protein/peptides. Results Isoflavone-free soy protein diet significantly reduced LPS-induced VCAM-1 mRNA and protein expression in aorta compared to CAS-fed mice. Reduced VCAM-1 expression in SPI − -fed mice also paralleled attenuated monocyte adhesion to vascular endothelium, a critical and primary processes during inflammation. Notably, VCAM-1 mRNA and protein expression in lesion-prone aortic arch was significantly reduced in apoE−/− mice fed SPI − for 5 weeks compared with CAS-fed mice. Moreover, dietary SPI − potently inhibited LPS-induced NF-κB activation and the subsequent upregulation of pro-inflammatory cytokines, including TNF-α, IL-6, IL-1β, and MCP-1. Interestingly, SPI − inhibited NF-κB-dependent inflammatory responses by targeting I-κB phosphorylation and AKT activation with no effect on MAP kinase pathway. Of the five putative soy peptides, four of the soy peptides inhibited LPS-induced VCAM-1, IL-6, IL-8, and MCP-1 protein expression in human vascular endothelial cells in vitro. Conclusions Collectively, our findings suggest that anti-inflammatory properties of component(s) of soy protein/peptides may be a possible mechanism for the prevention of chronic inflammatory diseases such as atherosclerosis.