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RGD‐peptide lunasin inhibits PI3‐kinase/Akt‐mediated NF‐κB activation in human and murine macrophages through interaction with αvβ3 integrins
Author(s) -
Cam Anthony,
Mejia Elvira Gonzalez
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1026.13
Subject(s) - integrin , protein kinase b , vitronectin , chemistry , receptor , pi3k/akt/mtor pathway , microbiology and biotechnology , signal transduction , biology , biochemistry
Regulation of aberrant macrophage activity under inflammatory conditions is critical in the prevention of cardiovascular disease (CVD). Integrin receptor α v β 3 is highly expressed on macrophages in atherosclerotic lesions and binds Arg‐Gly‐Asp (RGD) ligands. Lunasin is a food derived peptide that contains a RGD cell adhesion motif. The objective was to comparatively determine the effect of lunasin on pro‐inflammatory markers from LPS‐induced RAW 264.7 murine and THP‐1 human macrophages and its role on α v β 3 integrins, important mediators of PI3K/Akt activation of NF‐κB. Lunasin significantly inhibited NO (IC 50 = 41 μM; <10 μM), iNOS (IC 35 = 36 μM; IC 50 <10 μM), COX‐2 (IC 50 = 31 μM; <10 μM) and p‐Akt (IC 35 = 29 μM; IC 50 = 11 μM) in murine and human macrophages, respectively. In RAW 264.7, lunasin significantly inhibited PGE 2 (IC 50 = 48 μM) and reduced nuclear NF‐κB subunits p65 and p50 by 26% and 43% at 50 μM, respectively. Lunasin significantly reduced p‐p65 (IC 50 <10 μM) and α v β 3 integrin expression (IC 50 = 10 μM) in THP‐1. Vitronectin, a ligand of α v β 3 integrin, internalizes and increases expression of pro‐inflammatory markers, whereas a PI3K inhibitor attenuated these effects. After treatment of both cell lines with lunasin, co‐immunoprecipitation confirmed direct interaction between lunasin and α v β 3 integrin. Lunasin reduced integrin‐mediated inflammatory responses and has potential in the prevention of CVD. Grant Funding Source : USDA