Toll-like receptor 4-dependent activation of macrophages by polysaccharide isolated from the radix of Platycodon grandiflorum

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Title
Toll-like receptor 4-dependent activation of macrophages by polysaccharide isolated from the radix of Platycodon grandiflorum
Author(s)
Yeo Dae Yoon; Sang Bae Han; Jong Soon KangChang Woo Lee; Song Kyu Park; Hyun Sun Lee; J S Kang; Hwan Mook Kim
Bibliographic Citation
International Immunopharmacology, vol. 3, no. 13, pp. 1873-1882
Publication Year
2003
Abstract
Platycodon grandiflorum, a traditional oriental herbal medicine, is known to have immunostimulatory and antitumor effects. PG, a polysaccharide isolated from P. grandiflorum, has been reported to activate macrophages and B cells. Here, we investigated the membrane receptor and intracellular signaling responsible for the activation of macrophages by PG. PG induced the production of nitric oxide (NO) and the mRNA expression of iNOS in RAW 264.7 cells. To investigate the membrane receptor involved in the activation of NO production, we examined the effect of PG on the production of NO in mouse peritoneal macrophages isolated from wild type C3H/HeN and functional Toll-like receptor 4 (TLR4)-deficient C3H/HeJ mice. PG induced NO production by macrophages isolated from C3H/HeN mice, but had no effect on NO production by macrophages isolated from C3H/HeJ mice. Moreover, monoclonal antibodies directed to TLR4 blocked PG-mediated induction of NO production. In addition, LBP and sCD14 was also found to be involved in the activation of NO production by PG. To further investigate, we examined the effect of PG on the activation of DNA binding of NF-κB, which is a downstream transcriptional regulator of TLR4. PG caused degradation of IκB and activation of DNA binding of NF-κB. In addition, TPCK, a specific NF-κB inhibitor, abolished PG-mediated induction of DNA binding of NF-κB, production of NO and mRNA expression of iNOS, demonstrating the involvement of NF-κB in PG-mediated macrophage activation. Taken together, these results suggest that PG-mediated induction of NO production and iNOS mRNA expression in macrophages is mediated, at least in part, by TLR4/NF-κB signaling pathway.
Keyword
macrophageNF-κBnitric oxideplatycodon grandiflorumtoll-like receptor
ISSN
1567-5769
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.intimp.2003.09.005
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of Bioinfrastructure > Laboratory Animal Resource Center > 1. Journal Articles
Ochang Branch Institute > Natural Medicine Research Center > 1. Journal Articles
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