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Citreorosein inhibits degranulation and leukotriene C4 generation through suppression of Syk pathway in mast cells

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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 C4 (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 Cγ (PLCγ), mobilization of intracellular Ca2+, phosphatidylinositol 3-kinase (PI3K), Akt, MAP kinases (MAPKs), translocation of phospho-phospholipase A2 (PLA2) 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.

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Acknowledgments

This study was supported by the National Research Foundation of Korea Grant funded by the Korea government (NRF-2010-616-E00011 and MEST-2011-0006179).

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Authors and Affiliations

  1. College of Pharmacy, Yeungnam University, Gyeongsan, 712-749, Republic of Korea

    Yue Lu, Ying Li, Yurndong Jahng, Jong-Keun Son & Hyeun Wook Chang

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  1. Yue Lu
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  2. Ying Li
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  3. Yurndong Jahng
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  4. Jong-Keun Son
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  5. Hyeun Wook Chang
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Correspondence to Jong-Keun Son or Hyeun Wook Chang.

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Yue Lu and Ying Li contributed equally to this study.

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Lu, Y., Li, Y., Jahng, Y. et al. Citreorosein inhibits degranulation and leukotriene C4 generation through suppression of Syk pathway in mast cells. Mol Cell Biochem 365, 333–341 (2012). https://doi.org/10.1007/s11010-012-1273-3

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  • DOI: https://doi.org/10.1007/s11010-012-1273-3

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