Citreorosein Inhibits Production of Proinflammatory Cytokines by Blocking Mitogen Activated Protein Kinases, Nuclear Factor-kappa B and Activator Protein-1 Activation in Mouse Bone Marrow-Derived Mast Cells

Title
Citreorosein Inhibits Production of Proinflammatory Cytokines by Blocking Mitogen Activated Protein Kinases, Nuclear Factor-kappa B and Activator Protein-1 Activation in Mouse Bone Marrow-Derived Mast Cells
Author(s)
유예[유예]서석종[서석종]량경록지미연[지미연]황보경[황보경]권오균[권오균]정태욱[정태욱]곽충환[곽충환]권경민[권경민]Makoto Murakami[Makoto Murakami]장영동김철호[김철호]손종근장현욱
Keywords
POLYGONI-CUSPIDATI RADIX; TUMOR-NECROSIS-FACTOR; MEDIATOR RELEASE; HMC-1 CELLS; TNF-ALPHA; PATHWAYS; IL-6; MAPK; ERK; TRANSCRIPTION
Issue Date
201206
Publisher
PHARMACEUTICAL SOC JAPAN
Citation
BIOLOGICAL & PHARMACEUTICAL BULLETIN, v.35, no.6, pp.938 - 945
Abstract
Citreorosein (CIT), an anthraquinone component of Polygoni cuspidati (P. cuspidati) radix, suppressed gene expression of proinflammatory cytokines including tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-1 beta in mouse bone marrow-derived mast cells (BMMCs) stimulated with phorbol 12-myristate 13-acetate (PMA) plus the calcium ionophore A23187. To investigate the molecular mechanisms underlying CIT inhibition of the pro-inflammatory cytokine production, its effects on the activation of both nuclear factor-kappa B (NF-kappa B) and mitogen-activated protein kinases (MAPKs) were assessed. CIT attenuated phosphorylation of the MAPKs including extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAP kinase and c-Jun NH2-terminal kinase (JNK). Furthermore, CIT strongly inhibited DNA binding activity of NF-kappa B through the inhibition of phosphorylation and degradation of inhibitor of kappaB (1 kappa B) as well as activator protein-1 (AP)-1 through the reduction of phosphorylation of c-Jun. These results demonstrate that CIT inhibits proinflammatory cytokines production through the inhibition of both MAPKs and AKT-mediated 1 kappa B kinase (IKK) phosphorylation and subsequent inhibition of transcription factor NF-kappa B activation, thereby attenuating the production of proinflammatory cytokines.
URI
http://hdl.handle.net/YU.REPOSITORY/28116
ISSN
0918-6158
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약학대학 > 약학부 > Articles
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