title: Ginsenoside Rh2-B1 stimulates cell proliferation and IFN-γ production by activating the p38 MAPK and ERK-dependent signaling pathways in CTLL-2 cells.
abstract: BACKGROUND
  Ginsenoside Rh2, an active component of ginseng, exhibits immunoregulatory and anti-inflammatory properties. Rh2-B1, a sulfated derivative, was prepared to enhance its water solubility. We studied the effect of Rh2-B1 on CTLL-2, a CD8⁺ cytotoxic T cell line that was known for protecting against viral infection.
  
  
  OBJECTIVE
  We aimed to investigate the effect of Rh2-B1 on interferon (IFN)-γ production and cell proliferation and its possible mechanism.
  
  
  METHODS
  Enzyme-linked immunosorbent assay (ELISA) was employed to analyze the IFN-γ concentration of the whole blood and the supernatant of CTLL-2 cell culture. Cell proliferation assay was conducted using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Western blots were used to evaluate changes in signal transduction pathways in CTLL-2 cells.
  
  
  RESULTS
  Rh2-B1 was able to enhance IFN-γ production from whole blood culture of Balb/c mice. We then evaluated the effect of Rh2-B1 on a cytotoxic T cell line, CTLL-2 for cell proliferation, IFN-γ production and its molecular mechanism. Rh2-B1 promoted cell proliferation and IFN-γ production of CTLL-2 cells. It also induced activation of p38 mitogen-activated protein kinase (MAPK) and extracellular-signal-regulated kinases (ERK), but inhibited p56 Lck and transducer and activator of transcription 5 (STAT5) expression. The effect was blocked by the specific p38 MAPK inhibitor SB203580 and ERK inhibitor U0126.
  
  
  CONCLUSIONS
  Rh2-B1 could stimulate cell proliferation and IFN-γ production by activating the p38 MAPK- and ERK-dependent signaling pathways in cytotoxic T cells. This may be a novel medicine for treatment of viral infections.
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University , Changchun, Jilin , China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Lv
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Yi
authors.forename: Hai-Qing
authors.initials: HQ
authors.lastname: Shen
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Zhang
authors.forename: Hai-Bing
authors.initials: HB
authors.lastname: Dong
authors.forename: Shuai-Cheng
authors.initials: SC
authors.lastname: Wu
authors.forename: Fang
authors.initials: F
authors.lastname: Xia
authors.forename: Xun
authors.initials: X
authors.lastname: Guo
authors.forename: Xu-Bin
authors.initials: XB
authors.lastname: Wei
authors.forename: Ben-Dong
authors.initials: BD
authors.lastname: Fu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D036145:Ginsenosides / Q000494:pharmacology*; D007371:Interferon-gamma / Q000276:immunology*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D014777:Virus Diseases / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology*
chemical_list: D000893:Anti-Inflammatory Agents; D036145:Ginsenosides; C055305:ginsenoside Rh2; C093162:ginsenoside B; D007371:Interferon-gamma; D048051:p38 Mitogen-Activated Protein Kinases