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Inhibitory effects of phloretin on thrombin induction of protease activated receptor and inflammatory cytokines
Author(s) -
Kim MinSoo,
Kang Young-Hee
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.1025.31
Subject(s) - phloretin , thrombin , chemistry , proinflammatory cytokine , monocyte , inflammation , receptor , pharmacology , biochemistry , immunology , biology , platelet
Beyond its key role in the dynamic process of physiological and pathological coagulation as a proteolytic enzyme, thrombin possesses a distinct pro‐inflammatory activity, which may influence the onset and progression of atherosclerosis. This study investigated with THP‐1 monocytes that 1–20 μM phloretin, a dihydrochalcone found in apple tree leaves, attenuated thrombin induction of protease activated receptor (PAR) and inflammatory cytokines being involved in early atherosclerosis. This study found that thrombin promoted its membrane receptor PAR‐1 expression, which was blunted by phloretin nontoxic at 1–20 μM. The thrombin induction of plasminogen activator inhibitor‐1, a serine protease inhibitor, was dose‐dependently attenuated by treating phloretin to monocytes. In addition, the secretion of the cytokines of monocyte chemotactic protein‐1, interleukin (IL)‐6 and IL‐8, all responsible for vascular inflammation, was enhanced by thrombin. Such secretion was dampened by submicromolar phloretin, as evidenced by Western blotting and enzyme‐linked immunosorbent assay. These results demonstrate that phloretin retarded the expression and secretion of PAR‐1, PAI‐1 and inflammatroy cytokines in thrombin‐experienced monocytes. Thus, phloretin may qualify as a potential agent targeting thrombin exerting pro‐atherogenic actions associated with vascular inflammation.