title: Toll-like receptor 4-mediated immunoregulation by the aqueous extract of Mori Fructus.
abstract: 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.
authors.affiliation: Department of Infection Biology, Zoonosis Research Center, Wonkwang University School of Medicine, Iksan, Chonbuk 570-749, South Korea.
authors.forename: Xin-Ying
authors.initials: XY
authors.lastname: Yang
authors.forename: Gil-Soon
authors.initials: GS
authors.lastname: Park
authors.forename: Moo Hyung
authors.initials: MH
authors.lastname: Lee
authors.forename: In Ae
authors.initials: IA
authors.lastname: Chang
authors.forename: Youn Chul
authors.initials: YC
authors.lastname: Kim
authors.forename: Sung Yeon
authors.initials: SY
authors.lastname: Kim
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Yong Gab
authors.initials: YG
authors.lastname: Yun
authors.forename: Hyun
authors.initials: H
authors.lastname: Park
mesh_terms: 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
chemical_list: 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