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(2R,3R)‐2‐(3′,4′‐dihydroxybenzyl)‐3‐(3″,4″‐dimethoxybenzyl)butyrolactone(PP‐6) suppresses fMLP‐induced superoxide production by inhibiting fMLP‐receptor binding in human neutrophils
Author(s) -
Liao ChangHui,
Chen IhSheng,
Huang YiJia,
Tseng ChingPing,
Day YuanJi,
Lin YinChou
Publication year - 2008
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.22.1_supplement.910.8
Subject(s) - superoxide , chemistry , chemotaxis , intracellular , n formylmethionine leucyl phenylalanine , phosphorylation , receptor , nadph oxidase , reactive oxygen species , microbiology and biotechnology , biochemistry , biophysics , biology , enzyme
This study investigated the mechanism underlying the inhibiting effect of PP‐6, a lignan from Piper philippinum , on superoxide anion production induced by the chemotactic peptide fMLP in human neutrophils. Human neutrophils were stimulated with fMLP (1 μM), PMA (100 nM) or LTB 4 (1 μM) and induced superoxide anion release. PP‐6 inhibited fMLP‐induced superoxide anion production in a concentration‐dependent manner with an IC 50 value of 0.3±0.1 μM. Intracellular signaling caused by fMLP, PMA or LTB 4 were evaluated. PP‐6 inhibited fMLP‐induced intracellular calcium mobilization and ERK, Akt and p38 phosphorylation. Moreover, PP‐6 inhibited fMLP‐induced Mac‐1 expression without affecting this caused by LTB 4 or PMA. PP‐6 did not increase cAMP level in human neutrophils. PP‐6 did not inhibit superoxide anion production by NaF, the target of the inhibitory action of PP‐6 appears to be a component of the signal transduction pathway upstream of G‐protein. PP‐6 inhibited FITC‐fMLP binding to neutrophils in a concentration‐dependent manner with an IC 50 of 1.5±0.2 μM. PP‐6 did not bring a parallel shift in the concentration response of fMLP‐induced superoxide anion. Additionally, the inhibiting effect of PP‐6 on fMLP induced superoxide anion was reversed when PP‐6 was washed out. These experimental results suggest that PP‐6 exerts non‐competitive and reversible antagonistic effect on fMLP receptor.