title: Molecular mechanism of macrophage activation by red ginseng acidic polysaccharide from Korean red ginseng.
abstract: 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.
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Se Eun
authors.initials: SE
authors.lastname: Byeon
authors.forename: Jaehwi
authors.initials: J
authors.lastname: Lee
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Kim
authors.forename: Woo Seok
authors.initials: WS
authors.lastname: Yang
authors.forename: Yi-Seong
authors.initials: YS
authors.lastname: Kwak
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Eui Su
authors.initials: ES
authors.lastname: Choung
authors.forename: Man Hee
authors.initials: MH
authors.lastname: Rhee
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
mesh_terms: D051698:Activating Transcription Factor 2; D000818:Animals; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D015151:Immunoblotting; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D005894:Panax / Q000737:chemistry*; D011134:Polysaccharides / Q000494:pharmacology*; D020710:RGS Proteins / Q000172:deficiency / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D051698:Activating Transcription Factor 2; C497106:Atf2 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D016328:NF-kappa B; D011134:Polysaccharides; D020710:RGS Proteins; C105345:Rgs2 protein, mouse; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D018808:Transcription Factor AP-1