title: Citreorosein inhibits degranulation and leukotriene C₄ generation through suppression of Syk pathway in mast cells.
abstract: The aim of this study was to evaluate whether citreorosein (CIT), a naturally occurring anthraquinone isolated from Polygoni cuspidati (P. cuspidati) radix, modulates degranulation and 5-lipoxygenase (5-LO)-dependent leukotriene C(4) (LTC(4)) generation in mast cells. Cit suppresses both degranulation and the generation of LTC(4) in a dose-dependent manner in stem cell factor (SCF)-mediated mouse bone marrow-derived mast cells (BMMCs). With regard to its molecular mechanism of action, we investigated the effects of CIT on intracellular signaling and mast cell activation employing BMMCs. Binding of SCF to c-Kit on mast cell membranes induced increases in intrinsic tyrosine kinase Syk activity and activation of multiple downstream events including phosphorylation of phospholipase Cγ (PLCγ), mobilization of intracellular Ca(2+), phosphatidylinositol 3-kinase (PI3K), Akt, MAP kinases (MAPKs), translocation of phospho-phospholipase A(2) (PLA(2)) and 5-LO. The results from the biochemical analysis demonstrate that CIT attenuates degranulation and LTC(4) generation through the suppression of multiple step signaling and would be beneficial for the prevention of allergic inflammation.
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Yue
authors.initials: Y
authors.lastname: Lu
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Yurndong
authors.initials: Y
authors.lastname: Jahng
authors.forename: Jong-Keun
authors.initials: JK
authors.lastname: Son
authors.forename: Hyeun Wook
authors.initials: HW
authors.lastname: Chang
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation; D002478:Cells, Cultured; D004789:Enzyme Activation; D005260:Female; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D017997:Leukotriene C4 / Q000378:metabolism*; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D051966:Phospholipase C gamma / Q000378:metabolism; D054510:Phospholipases A2, Cytosolic / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000502:physiology; D000072377:Syk Kinase; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
chemical_list: D000880:Anthraquinones; D000893:Anti-Inflammatory Agents; D047908:Intracellular Signaling Peptides and Proteins; D019089:Stem Cell Factor; D017997:Leukotriene C4; D001094:Arachidonate 5-Lipoxygenase; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D020928:Mitogen-Activated Protein Kinases; D054510:Phospholipases A2, Cytosolic; D051966:Phospholipase C gamma; D001619:beta-N-Acetylhexosaminidases; C540595:citreorosein; D002118:Calcium