title: Ginsenoside Rg1 regulates innate immune responses in macrophages through differentially modulating the NF-κB and PI3K/Akt/mTOR pathways.
abstract: Ginsenoside Rg1 is one of the major active components of ginseng, which has been shown to regulate the immune response of hosts. However, the mechanism underlying the immunomodulatory effect of Rg1 is incompletely understood. In this study, we aimed to explore whether and how Rg1 regulates the innate immune response in macrophages. The results showed that Rg1 treatment significantly increased tumor necrosis factor (TNF)-α but decreased interleukin-6 (IL-6) protein expression in both lipopolysaccharide (LPS)-activated RAW 264.7 cells and mouse peritoneal macrophages. However, Rg1 reduced the mRNA levels of both cytokines in LPS-activated macrophages, which might be a consequence of decreased activation of IκB and nuclear factor-κB (NF-κB). Importantly, Rg1 treatment further promoted LPS-induced activation of the Akt/mechanistic target of rapamycin (mTOR) pathway, which is critical for controlling protein translation. The elevated Akt/mTOR signaling was likely responsible for increased production of TNF-α protein at the translational level, as suppression of this pathway by LY294002, an inhibitor of the upstream phosphatidylinositol 3-kinase (PI3K), abrogated such an enhancement of TNF-α protein expression even though its mRNA levels were conversely increased. These findings highlight a novel mechanism for Rg1 to regulate the innate immune response in macrophages through differentially modulating the NF-κB and PI3K/Akt/mTOR pathways.
authors.affiliation: Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou 510630, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Dermatology, Chinese Academy of Medical Sciences, Nanjing 210042, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou 510630, China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510630, China.
authors.forename: Li-Hui
authors.initials: LH
authors.lastname: Xu
authors.affiliation: Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou 510630, China.
authors.forename: Dong-Yun
authors.initials: DY
authors.lastname: Ouyang
authors.affiliation: Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou 510630, China.
authors.forename: Kun-Peng
authors.initials: KP
authors.lastname: Liu
authors.affiliation: Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou 510630, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou 510630, China.
authors.forename: Jian
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou 510630, China. Electronic address: thexh@jnu.edu.cn.
authors.forename: Xian-Hui
authors.initials: XH
authors.lastname: He
mesh_terms: D000818:Animals; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D036145:Ginsenosides / Q000494:pharmacology*; D007113:Immunity, Innate / Q000187:drug effects*; D056747:Immunomodulation; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009025:Morpholines / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D002867:Chromones; D036145:Ginsenosides; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009025:Morpholines; D016328:NF-kappa B; D000081082:Phosphoinositide-3 Kinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C035054:ginsenoside Rg1
keywords: Ginsenoside Rg1; Interleukin-6; Lipopolysaccharide; Macrophages; Tumor necrosis factor-α; mTOR