Molecular Mechanism of Macrophage Activation by Red Ginseng Acidic Polysaccharide from Korean Red Ginseng

Red ginseng acidic polysaccharide (RGAP), isolated from Korean red ginseng, displays immunostimulatory and antitumor activities. Even though numerous studies have been reported, the mechanism as to how RGAP is able to stimulate the immune response is not clear. In this study, we aimed to explore the...

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Main Authors: Se Eun Byeon, Jaehwi Lee, Ji Hye Kim, Woo Seok Yang, Yi-Seong Kwak, Sun Young Kim, Eui Su Choung, Man Hee Rhee, Jae Youl Cho
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2012/732860
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author Se Eun Byeon
Jaehwi Lee
Ji Hye Kim
Woo Seok Yang
Yi-Seong Kwak
Sun Young Kim
Eui Su Choung
Man Hee Rhee
Jae Youl Cho
author_facet Se Eun Byeon
Jaehwi Lee
Ji Hye Kim
Woo Seok Yang
Yi-Seong Kwak
Sun Young Kim
Eui Su Choung
Man Hee Rhee
Jae Youl Cho
author_sort Se Eun Byeon
collection DOAJ
description Red ginseng acidic polysaccharide (RGAP), isolated from Korean red ginseng, displays immunostimulatory and antitumor activities. Even though numerous studies have been reported, the mechanism as to how RGAP is able to stimulate the immune response is not clear. In this study, we aimed to explore the mechanism of molecular activation of RGAP in macrophages. RGAP treatment strongly induced NO production in RAW264.7 cells without altering morphological changes, although the activity was not strong compared to LPS-induced dendritic-like morphology in RAW264.7 cells. RGAP-induced NO production was accompanied with enhanced mRNA levels of iNOS and increases in nuclear transcription factors such as NF-κB, AP-1, STAT-1, ATF-2, and CREB. According to pharmacological evaluation with specific enzyme inhibitors, Western blot analysis of intracellular signaling proteins and inhibitory pattern using blocking antibodies, ERK, and JNK were found to be the most important signaling enzymes compared to LPS signaling cascade. Further, TLR2 seems to be a target surface receptor of RGAP. Lastly, macrophages isolated from RGS2 knockout mice or wortmannin exposure strongly upregulated RGAP-treated NO production. Therefore, our results suggest that RGAP can activate macrophage function through activation of transcription factors such as NF-κB and AP-1 and their upstream signaling enzymes such as ERK and JNK.
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spelling doaj-art-ac405694eb50429fa83c0b8bb9f5e6492025-02-03T00:59:32ZengWileyMediators of Inflammation0962-93511466-18612012-01-01201210.1155/2012/732860732860Molecular Mechanism of Macrophage Activation by Red Ginseng Acidic Polysaccharide from Korean Red GinsengSe Eun Byeon0Jaehwi Lee1Ji Hye Kim2Woo Seok Yang3Yi-Seong Kwak4Sun Young Kim5Eui Su Choung6Man Hee Rhee7Jae Youl Cho8Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of KoreaCollege of Pharmacy, Chung-Ang University, Seoul 122-704, Republic of KoreaDepartment of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of KoreaDepartment of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of KoreaKorea Ginseng Corporation, Central Research Institute, Daejeon 305-805, Republic of KoreaDepartment of Efficacy Screening, Hongcheon Institute of Medicinal Herb, Hongcheon 250-930, Republic of KoreaDepartment of Natural Product Resources, DanjoungBio, Wonju 220-842, Republic of KoreaCollege of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of KoreaDepartment of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of KoreaRed ginseng acidic polysaccharide (RGAP), isolated from Korean red ginseng, displays immunostimulatory and antitumor activities. Even though numerous studies have been reported, the mechanism as to how RGAP is able to stimulate the immune response is not clear. In this study, we aimed to explore the mechanism of molecular activation of RGAP in macrophages. RGAP treatment strongly induced NO production in RAW264.7 cells without altering morphological changes, although the activity was not strong compared to LPS-induced dendritic-like morphology in RAW264.7 cells. RGAP-induced NO production was accompanied with enhanced mRNA levels of iNOS and increases in nuclear transcription factors such as NF-κB, AP-1, STAT-1, ATF-2, and CREB. According to pharmacological evaluation with specific enzyme inhibitors, Western blot analysis of intracellular signaling proteins and inhibitory pattern using blocking antibodies, ERK, and JNK were found to be the most important signaling enzymes compared to LPS signaling cascade. Further, TLR2 seems to be a target surface receptor of RGAP. Lastly, macrophages isolated from RGS2 knockout mice or wortmannin exposure strongly upregulated RGAP-treated NO production. Therefore, our results suggest that RGAP can activate macrophage function through activation of transcription factors such as NF-κB and AP-1 and their upstream signaling enzymes such as ERK and JNK.http://dx.doi.org/10.1155/2012/732860
spellingShingle Se Eun Byeon
Jaehwi Lee
Ji Hye Kim
Woo Seok Yang
Yi-Seong Kwak
Sun Young Kim
Eui Su Choung
Man Hee Rhee
Jae Youl Cho
Molecular Mechanism of Macrophage Activation by Red Ginseng Acidic Polysaccharide from Korean Red Ginseng
Mediators of Inflammation
title Molecular Mechanism of Macrophage Activation by Red Ginseng Acidic Polysaccharide from Korean Red Ginseng
title_full Molecular Mechanism of Macrophage Activation by Red Ginseng Acidic Polysaccharide from Korean Red Ginseng
title_fullStr Molecular Mechanism of Macrophage Activation by Red Ginseng Acidic Polysaccharide from Korean Red Ginseng
title_full_unstemmed Molecular Mechanism of Macrophage Activation by Red Ginseng Acidic Polysaccharide from Korean Red Ginseng
title_short Molecular Mechanism of Macrophage Activation by Red Ginseng Acidic Polysaccharide from Korean Red Ginseng
title_sort molecular mechanism of macrophage activation by red ginseng acidic polysaccharide from korean red ginseng
url http://dx.doi.org/10.1155/2012/732860
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