title: Pseudolaric acid B inhibits T-cell mediated immune response in vivo via p38MAPK signal cascades and PPARγ activation.
abstract: OBJECTIVE
  Pseudolaric acid B (PAB) has been prescribed for its potent immunomodulatory effect. However, the detail of mechanism remains to be demonstrated. The purpose of this study is to further clarify the mechanism of PAB on T-cell mediated immune response in vivo.
  
  
  METHODS
  Investigations were carried to ascertain the pharmacological effect of PAB in a delayed-type hypersensitivity (DTH) mouse model of T-cell mediated immune response. Histological assessment was examined by hematoxylin and eosin staining. Affymetrix GeneChip® Mouse Genome 430 2.0 arrays were employed to evaluate the expression profile of PAB. Western blot was performed to detect p38MAPK signal cascades, including p38MAPK, ATF-2, MK2, and HSP27. Finally, TNF-α level was analyzed by ELISA, and Jurkat T cells were treated with PAB to determine its role on PPARγ activation using a reporter gene assay.
  
  
  RESULTS
  The results showed that PAB (5, 10, and 20mg/kg) could lead to a marked improvement for ear swelling and inflammatory infiltrate in DTH mice dose-dependently. According to the associated biological pathways from microarray analysis, PAB resulted in the restoration of abnormal immune-related gene expression linked to MAPK and PPAR signaling pathways. Moreover, PAB inhibited the activation of p38MAPK, ATF-2, MK2, and HSP27 significantly, as well as the production of TNF-α, which was reversed by GW9662, a specific antagonist for PPARγ. In addition, treatment with PAB also increased the transcriptional activity of PPARγ in a dose-dependent manner.
  
  
  CONCLUSIONS
  These results provide us with novel insights into pharmacological action of PAB as a potential immunomodulator for the treatment of immune-related diseases.
authors.affiliation: Department of Pathogen Biology and Immunology, Logistics University of the Chinese People's Armed Police Force, Tianjin, PR China; Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Logistics University of the Chinese People's Armed Police Force, Tianjin, PR China. Electronic address: tanli20042001@163.com.
authors.forename: Tan
authors.initials: T
authors.lastname: Li
authors.affiliation: Pingjin Hospital, Logistics University of the Chinese People's Armed Police Forces, Tianjin, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Logistics University of the Chinese People's Armed Police Force, Tianjin, PR China; Pingjin Hospital, Logistics University of the Chinese People's Armed Police Forces, Tianjin, PR China.
authors.forename: Ji-hong
authors.initials: JH
authors.lastname: Zhao
authors.affiliation: Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Logistics University of the Chinese People's Armed Police Force, Tianjin, PR China; Pingjin Hospital, Logistics University of the Chinese People's Armed Police Forces, Tianjin, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Logistics University of the Chinese People's Armed Police Force, Tianjin, PR China.
authors.forename: Yu-ming
authors.initials: YM
authors.lastname: Li
authors.affiliation: Department of Pharmacognosy and Pharmaceutics, Logistics University of the Chinese People's Armed Police Force, Tianjin, PR China; Tianjin Key Laboratory for Prevention and Control of Occupational and Environmental Hazard, Logistics University of the Chinese People's Armed Police Force, Tianjin, PR China. Electronic address: chenhongtian06@163.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D004139:Dinitrofluorobenzene / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology*; D004487:Edema / Q000188:drug therapy / Q000276:immunology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000188:drug therapy / Q000276:immunology; D019169:Jurkat Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D047495:PPAR gamma / Q000187:drug effects* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects* / Q000235:genetics
chemical_list: D004224:Diterpenes; D047495:PPAR gamma; D014409:Tumor Necrosis Factor-alpha; C058391:pseudolaric acid B; D004139:Dinitrofluorobenzene; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Delayed-type hypersensitivity; Microarray; PPARγ; Pseudolaric acid B; p38MAPK