Citreorosein inhibits degranulation and leukotriene C-4 generation through suppression of Syk pathway in mast cells

Title
Citreorosein inhibits degranulation and leukotriene C-4 generation through suppression of Syk pathway in mast cells
Author(s)
장현욱유예[유예]이응[이응]장영동손종근
Keywords
CYTOSOLIC PHOSPHOLIPASE A(2); HEMATOPOIETIC GROWTH-FACTORS; KIT RECEPTOR LIGAND; PROTEIN-KINASE-C; POLYGONUM-CUSPIDATUM; ARACHIDONIC-ACID; SIGNAL-TRANSDUCTION; TYROSINE KINASE; FYN KINASE; IN-VIVO
Issue Date
201206
Publisher
SPRINGER
Citation
MOLECULAR AND CELLULAR BIOCHEMISTRY, v.365, no.1-2, pp.333 - 341
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 (LTC4) generation in mast cells. Cit suppresses both degranulation and the generation of LTC4 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 C gamma (PLC gamma), mobilization of intracellular Ca2+, 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 LTC4 generation through the suppression of multiple step signaling and would be beneficial for the prevention of allergic inflammation.
URI
http://hdl.handle.net/YU.REPOSITORY/28174http://dx.doi.org/10.1007/s11010-012-1273-3
ISSN
0300-8177
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약학대학 > 약학부 > Articles
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