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ARS Home » Southeast Area » Little Rock, Arkansas » Microbiome and Metabolism Research Unit » Research » Publications at this Location » Publication #308063
Title: Soy protein inhibits inflammation-induced VCAM-1 and inflammatory cytokine induction by inhibiting the NF-kappaB and AKT signaling pathway in apolipoprotein E-deficient mice

Author
item BURRIS, RAMONA - Arkansas Children'S Nutrition Research Center (ACNC)
item NG, HONG-PONG - University Arkansas For Medical Sciences (UAMS)
item NAGARAJAN, SHANMUGAM - University Arkansas For Medical Sciences (UAMS)

Submitted to: European Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/20/2013
Publication Date: 3/7/2014
Citation: Burris, R.L., Ng, H., Nagarajan, S. 2014. Soy protein inhibits inflammation-induced VCAM-1 and inflammatory cytokine induction by inhibiting the NF-kappaB and AKT signaling pathway in apolipoprotein E-deficient mice. European Journal of Nutrition. 53(1):135-148.

Interpretive Summary: Previous results from our laboratory have shown that a diet high in soy protein lowers the risk of developing atherosclerosis in animals. Soy protein also contains phytochemicals known as isoflavones and because it was not known if the protective effects of soy protein were due to the protein or the isoflavones, we demonstrated that isoflavone-free soy protein reduced atherosclerosis lesions as well. These studies suggested that the protein itself was responsible for preventing atherosclerosis, but the mechanisms by which the protein was protective against atherosclerosis was unknown. This current study was conducted to determine if the mechanism involved inflammation. Results from this study identified soy protein as a unique anti-inflammatory agent that may have a potential to prevent or treat inflammatory diseases such as atherosclerosis.

Technical Abstract: 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-kappaB-dependent inflammation mediators such as VCAM-1, TNF-a, and MCP-1 were determined in aorta and liver. NF-kappaB, 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-kappaB activation and the subsequent upregulation of pro-inflammatory cytokines, including TNF-a, IL-6, IL-1ß, and MCP-1. Interestingly, SPI(-) inhibited NF-'B-dependent inflammatory responses by targeting I-'B 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.