Echinacea-induced macrophage activation.
Public interest in Echinacea is growing rapidly. Unfortunately, there is little scientific evidence to support claims of efficacy of this widely used botanical, and little information about potential mechanism of action. This study examines the ability of Echinacea to upregulate macrophage function and begins to elucidate the mechanism of Echinacea-induced macrophage activation. Murine peritoneal macrophages were cultured with E. purpurea extracts enriched for plant polysaccharide (EP). ELISA was used to measure cytokine production. MAPKs were blocked using specific inhibitors, and Western blotting used to identify phosphorylated proteins involved in signal transduction. To examine in vivo efficacy, EP was administered orally and Listeria monocytogenes given i.v. Mice were sacrificed three days post-infection to determine bacterial load in the spleen. We demonstrate that an endotoxin-free EP extract activates the innate immune response, stimulating production of IL-6, TNF, IL-12, and NO from macrophages in vitro. Along with evidence of enhanced macrophage function, we found that oral EP reduces bacterial burden during infection by Listeria monocytogenes, demonstrating its efficacy in vivo. EP initiates a signaling cascade within macrophages through both TLR4-dependent and -independent mechanisms, involving ERK, p38 and JNK, and ultimately the activation of NF-kappaB.
Sullivan
Allyn M
AM
Departments of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
Laba
Jennifer G
JG
Moore
Jill A
JA
Lee
Timothy D G
TD
D000284:Administration, Oral; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D020900:Echinacea / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D007113:Immunity, Innate / Q000187:drug effects*; D007155:Immunologic Factors / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008088:Listeriosis / Q000276:immunology / Q000517:prevention & control; D008262:Macrophage Activation / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000494:pharmacology; D018517:Plant Roots; D011112:Polymyxin B / Q000494:pharmacology; D011134:Polysaccharides / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000187:drug effects / Q000378:metabolism
D016207:Cytokines; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D011134:Polysaccharides; D047428:Protein Kinase Inhibitors; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D020928:Mitogen-Activated Protein Kinases; D011112:Polymyxin B