Toll-like receptor 4-mediated immunoregulation by the aqueous extract of Mori Fructus.
The aqueous extract of Mori Fructus (MF) exerts a change of phenotype and a cytoprotective effect in macrophages. The present study was carried out to investigate the immunomodulating activity of MF on the expression of nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), co-stimulatory molecules and also interferon-gamma (IFN-gamma) in macrophages and splenocytes. Toll-like receptor 4 (TLR4) is a promising molecular target for immune-modulating drugs. It was hypothesized that one possible upstream signaling pathway leading to immunoregulation of MF may be mediated by TLRs. Multiple signaling molecules (NF-kappaB, ERK1/2, p38 and JNK) of the TLR4 signaling pathway were also detected. It was found that MF increased NO production and TNF-alpha secretion in RAW 264.7 and peritoneal macrophages, co-stimulatory molecules expression in peritoneal macrophages and IFN-gamma expression in splenocytes. Further studies indicated that MF could significantly induce the phosphorylation of signal molecules of MAPKs and the degradation of IkappaBalpha which finally led to the activation and nuclear translocation of nuclear factor-kappaB (NF-kappaB) for the target gene expression. All those notions disclosed that the aqueous extract MF is a new TLR4 activator, which induces a Th1 immune response as a consequence of induction of cytokines secretion, especially TNF-alpha and IFN-gamma.
Yang
Xin-Ying
XY
Department of Infection Biology, Zoonosis Research Center, Wonkwang University School of Medicine, Iksan, Chonbuk 570-749, South Korea.
Park
Gil-Soon
GS
Lee
Moo Hyung
MH
Chang
In Ae
IA
Kim
Youn Chul
YC
Kim
Sung Yeon
SY
Lee
Joo Young
JY
Yun
Yong Gab
YG
Park
Hyun
H
D000818:Animals; D002460:Cell Line; D005260:Female; D056747:Immunomodulation; D007371:Interferon-gamma / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D031625:Morus / Q000737:chemistry; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016328:NF-kappa B; D010936:Plant Extracts; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma; D020928:Mitogen-Activated Protein Kinases