title: Regulation of Th1/Th2 balance through OX40/OX40L signalling by glycyrrhizic acid in a murine model of asthma.
abstract: OBJECTIVE
  Glycyrrhizic acid (GA) has been reported to have attenuating airway inflammation effects in asthma mouse model. However, the potential molecular mechanisms by which GA exerts anti-inflammatory effects on ovalbumin (OVA)-induced allergic asthma have not been well elaborated.
  
  
  METHODS
  The effect of GA on OVA-sensitized and challenged mice was investigated. The effect of GA on anti-OX40 mAb stimulated splenocytes from asthma mice model was also examined.
  
  
  RESULTS
  In OVA-induced asthmatic mice, GA treatment prevented the decrease of T helper1 cytokine (interferon (IFN)-γ) and the increase of T helper2 cytokines (interleukin (IL)-4, IL-5, IL-13) in bronchoalveolar lavage fluid (BALF), reduced serum immunoglobulin (Ig)E and OVA-specific IgE levels, prohibited the protein and mRNA expression of OX40 and OX40 Ligand (OX40L) in lung tissues, and the expression of OX40 in CD4(+) T cells and OX40L in CD11b(+) monocytes and CD19(+) B cells in spleens in a dose-dependent manner compared with the vehicle treatment (all P < 0.05). Moreover, OVA significantly increased the activation of p38 mitogen-activated protein kinase (MAPK) in lung tissues, whereas GA and anti-OX40L mAb markedly reduced phosphorylation of p38 MAPK. In addition, GA could inhibit the T cell proliferation and modulate the balance of Th1/Th2 in anti-OX40 mAb stimulated CD4(+) T cells from asthmatic spleens (all P < 0.05).
  
  
  CONCLUSIONS
  GA may exert a therapeutic effect on OVA-induced experimental asthma partly by regulating the Th1/Th2 balance through suppressing OX40-OX40L signalling and p38 MAPK activity. GA may be a promising treatment for asthma.
authors.affiliation: Department of Respiratory and Critical Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China.|Department of Respiratory Medicine, The First People's Hospital of Wujiang, Suzhou, China.
authors.forename: Qiaozhen
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Respiratory Medicine, The First People's Hospital of Wujiang, Suzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Respiratory Medicine, The First People's Hospital of Wujiang, Suzhou, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Hu
authors.affiliation: Institute of Medical Biotechnology, Soochow University, Suzhou, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Respiratory and Critical Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lei
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Linfu
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Respiratory and Critical Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Jianan
authors.initials: J
authors.lastname: Huang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004195:Disease Models, Animal; D019695:Glycyrrhizic Acid / Q000378:metabolism / Q000494:pharmacology; D007073:Immunoglobulin E / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008168:Lung / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D053278:OX40 Ligand / Q000378:metabolism; D010047:Ovalbumin / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; C508598:IL4 protein, human; D018793:Interleukin-13; D053278:OX40 Ligand; C089251:TNFSF4 protein, human; D015847:Interleukin-4; D007073:Immunoglobulin E; D019695:Glycyrrhizic Acid; D010047:Ovalbumin; D048051:p38 Mitogen-Activated Protein Kinases
keywords: OX40; OX40 ligand; asthma; cytokine; glycyrrhizic acid