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  • Title: Activation of mitogen-activated protein kinases and AP-1 by polysaccharide isolated from the radix of Platycodon grandiflorum in RAW 264.7 cells.
    Author: Yoon YD, Kang JS, Han SB, Park SK, Lee HS, Kang JS, Kim HM.
    Journal: Int Immunopharmacol; 2004 Nov; 4(12):1477-87. PubMed ID: 15351317.
    Abstract:
    The root of Platycodon grandiflorum has been widely used for the treatment of various diseases in oriental medicine. Our previous study showed that the PG, a polysaccharide isolated from P. grandiflorum, activates macrophages via Toll-like receptor 4 (TLR4). However, the associated biological mechanisms are not fully understood. To elucidate the molecular mechanism responsible for the macrophage activation, we investigated the effect of PG on the activity of mitogen-activated protein kinases (MAPKs) and activator protein-1 (AP-1) in RAW 264.7 cells, a murine macrophage cell line. Treatment of RAW 264.7 cells with PG produced a marked induction of AP-1 DNA binding activity. Moreover, all three MAPKs were activated by PG, and PG-induced activation of MAPKs was abrogated by the treatment of PD98059, curcumin, and SB203580, specific inhibitors of MEK-1/2, stress-activated protein kinases/jun N-terminal kinase (SAPK/JNK), and p38 MAP kianse, respectively. The induction of AP-1 DNA binding activity by PG was also inhibited by these MAPK inhibitors. Moreover, supershift analysis identified that JunB and Fra-1 are major components involved in the PG-mediated induction of AP-1 DNA binding. Additionally, curcumin and SB203580 suppressed PG-induced production of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha), whereas PD98059 showed an inhibitory effect only on the TNF-alpha production. Taken together, these results suggest that macrophage activation by PG is mediated, at least in part, by MAPKs and AP-1.
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