The immunomodulator ginsan induces resistance to experimental sepsis by inhibiting Toll-like receptor-mediated inflammatory signals.
Ginsan, a polysaccharide extracted from Panax ginseng, has multiple immunomodulatory effects. In this study, we show that pretreatment of ginsan (25 mug/kg) protected mice from lethality induced by Staphylococcus aureus challenge. This survival benefit was associated with enhanced bacterial clearance from circulation, spleen and kidney. The phagocytic activity of macrophages treated with ginsan was significantly enhanced against S. aureus. However, the production of proinflammatory cytokines, such as TNF-alpha, IL-1beta, IL-6, IFN-gamma, IL-12, and IL-18, was markedly down-regulated in ginsan-treated mice compared with those of control-infected mice. The expression of Toll-like receptor (TLR) 2 and the adaptor molecule MyD88, which was greatly increased in septic macrophages, was significantly reduced by ginsan treatment in vitro. Similarly, the expression of phospho-JNK1/2, phospho-p38 MAPK, and NF-kappaB was decreased in the same culture system. These results illustrate that the antiseptic activity of ginsan can be attributed to enhanced bacterial clearance, and reduced proinflammatory cytokines via the TLR signaling pathway.
Ahn
Ji-Yeon
JY
Laboratory of Radiation Immunology, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
Choi
In-Soo
IS
Shim
Ji-Young
JY
Yun
Eun-Kyung
EK
Yun
Yeon-Sook
YS
Jeong
Gajin
G
Song
Jie-Young
JY
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D016207:Cytokines / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D015151:Immunoblotting; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020929:Mitogen-Activated Protein Kinase Kinases / Q000187:drug effects / Q000276:immunology; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D005894:Panax / Q000737:chemistry; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D010936:Plant Extracts / Q000627:therapeutic use; D011134:Polysaccharides / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000209:etiology / Q000517:prevention & control*; D013203:Staphylococcal Infections / Q000150:complications; D013211:Staphylococcus aureus; D051193:Toll-Like Receptors / Q000187:drug effects* / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D000893:Anti-Inflammatory Agents; D016207:Cytokines; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D010936:Plant Extracts; D011134:Polysaccharides; D051193:Toll-Like Receptors; C111520:ginsan; D020929:Mitogen-Activated Protein Kinase Kinases