Panax ginseng C.A. Mayer G115 modulates pro-inflammatory cytokine production in mice throughout the increase of macrophage toll-like receptor 4 expression during physical stress.
The effect of Panax ginseng C.A. Meyer G115 on inflammatory cytokine production and toll-like receptor 4 (TLR4) RNA expression was examined in mice during 4 weeks of swimming stress. Mice were assigned to four groups: (1) control (no exercise); (2) control-G115 (25 mg/kg/day p.o.); (3) stress (kept swimming for 60 min daily); and (4) stress-G115 (25 mg/kg/day p.o. and kept swimming for 60 min daily). Peritoneal macrophages were collected at rest each week. RNA was extracted and processed for real-time PCR. An aliquot of macrophages was lipopolysaccharide (LPS)-stimulated for TNF-alpha and IL-1beta production. Different expression patterns between untreated and treated groups, and between TLR2 and TLR4 were found. High levels of TLR4 expression in the control-G115 group were detectable significantly at the first, and at the second week (P<.01 and P<.001, respectively). In the stress group, TLR4 showed a peak at the first week (P<.001 vs. controls) and then decreased gradually. In the stress-G115 group, the levels of TLR4 expression increased gradually at the second week (P<.001 vs. controls) with a peak at the third week (P<.001). Levels of TLR4 expression at the fourth week had returned to the basal level. Levels of TLR2 expression were not affected by treatment in all groups. A significant increase of LPS-stimulated IL-1beta and TNF-alpha concentrations was present in trained animals with similar patterns of TLR4 expression. These results support the hypothesis that enhancement of the production of pro-inflammatory cytokine can be linked to an increased expression of TLR4 on macrophages. Moreover, G115 increases the expression of TLR4 and the release of cytokines with a different pattern compared to the stressed alone group.
Department of Pharmacology, Chemotherapy and Toxicology, Faculty of Medicine, University of Milan, via Vanvitelli 32, 20129 Milan, Italy.
Marilou
M
Pannacci
Valeria
V
Lucini
Federica
F
Colleoni
Cataldo
C
Martucci
Silvia
S
Grosso
Paola
P
Sacerdote
Francesco
F
Scaglione
D000704:Analysis of Variance; D000818:Animals; D016207:Cytokines; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D005894:Panax; D005082:Physical Exertion / Q000502:physiology*; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D012313:RNA / Q000032:analysis; D011897:Random Allocation; D018709:Statistics, Nonparametric; D013312:Stress, Physiological / Q000276:immunology* / Q000378:metabolism; D013550:Swimming / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D010936:Plant Extracts; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D012313:RNA