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This study investigates the effect and the underlying mechanism of 5\u2010hydroxy\u20102\u2010(4\u2010hydroxy\u20103\u2010methoxyphenyl)\u20103,7\u2010dimethoxy\u20104H\u2010chromen\u20104\u2010one (MSF\u20102), a lignan extracted from the fruit of <jats:italic>Melicope Semecarprifolia<\/jats:italic>, on fMLP\u2010induced respiratory burst in human neutrophils and suggests a possible therapeutic approach to ameliorate disease associated with neutrophil hyperactivation. MSF\u20102 inhibited fMLP\u2010induced neutrophil superoxide anion production, cathepsin G release and migration in human neutrophils isolated from healthy volunteers, reflecting inhibition of phosphatidylinositol 3\u2010kinase (PI3K) activation. Specifically, PI3K\/AKT activation results in migration, degranulation and superoxide anion production in neutrophils. MSF\u20102 suppresses PI3K activation and phosphatidylinositol (3,4,5)\u2010trisphosphate (PIP3) production, and consequently inhibits downstream activation of PDK1 and AKT. Further, PI3K also stimulates respiratory burst via PLC\u2010dependent elevation of intracellular calcium. MSF\u20102 reduces fMLP\u2010mediated PLC\u03b32 activation and intracellular calcium accumulation notably through extracellular calcium influx in a PI3K and PLC\u2010dependent manner. However, MSF\u20102 is not a competitive or allosteric antagonist of fMLP. Additionally, in an in vivo study, MSF\u20102 prevents fMLP\u2010induced neutrophil infiltration and inflammation in mice. In conclusion, MSF\u20102 opposes fMLP\u2010mediated neutrophil activation and inflammation by inhibiting PI3K activation and subsequent activation of AKT and PLC\u03b32. J. Cell. Physiol. 226: 1519\u20131530, 2011. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.22481","type":"journal-article","created":{"date-parts":[[2010,10,13]],"date-time":"2010-10-13T14:21:28Z","timestamp":1286979688000},"page":"1519-1530","source":"Crossref","is-referenced-by-count":6,"title":["5\u2010hydroxy\u20102\u2010(4\u2010hydroxy\u20103\u2010methoxyphenyl)\u20103,7\u2010dimethoxy\u20104H\u2010chromen\u20104\u2010one (MSF\u20102) suppresses fMLP\u2010mediated respiratory burst in human neutrophils by inhibiting phosphatidylinositol 3\u2010kinase activity"],"prefix":"10.1002","volume":"226","author":[{"given":"Chang\u2010Hui","family":"Liao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jih\u2010Jung","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jieru 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