title: Anti-inflammatory effect of transduced PEP-1-cyclophilin A in Raw264.7 cells and 12-O-tetradecanoylphorbol-13-acetate-induced mice.
abstract: OBJECTIVE
  Cyclophilin A (CypA) is an immunophilin that acts as a receptor for the immunosuppressant drug cyclosporine A (CsA). CypA has emerged as a potential drug target for several inflammatory diseases, although the details of its mechanism are unclear. We examined the protective effects of CypA on inflammation in Raw 264.7 cells and animal models.
  
  
  METHODS
  A human CypA gene was fused with a protein transduction domain, PEP-1 peptide, to construct a cell permeable PEP-1-CypA protein. The protein expression level of cyclooxygenase-2 (COX-2) and cytokines was detected by Western blot, ELISA and mRNA level of COX-2 and cytokines were measured by RT-PCR. The nuclear factor-kappa B (NF-kB) and mitogen-activated protein kinase (MAPK) activation were analyzed by Western blot and electrophoretic mobility shift assay. Skin inflammation was detected with immunohistochemistry.
  
  
  RESULTS
  Transduced PEP-1-CypA protein markedly inhibited lipopolysaccharide- and 12-O-tetradecanoyl phorbol-13-acetate-induced expression levels of COX-2 as well as pro-inflammatory cytokine levels in vitro and in vivo. Furthermore, transduced PEP-1-CypA protein resulted in a significant reduction in the activation of NF-kB and MAPK.
  
  
  CONCLUSIONS
  The results indicate that PEP-1-CypA inhibits inflammatory response cytokines and enzymes by blocking NF-kB and MAPK activation upon stimulation of inflammation in vitro and in vivo. PEP-1-CypA protein may potentially be used as a therapeutic agent against skin diseases-related inflammation.
authors: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
authors: Min Jung
authors: MJ
authors: Lee
authors: Dae Won
authors: DW
authors: Kim
authors: Eun Jeong
authors: EJ
authors: Sohn
authors: Hoon Jae
authors: HJ
authors: Jeong
authors: Min Jea
authors: MJ
authors: Shin
authors: Hye Won
authors: HW
authors: Kang
authors: Eun Hee
authors: EH
authors: Ahn
authors: Soon Won
authors: SW
authors: Kwon
authors: Young Nam
authors: YN
authors: Kim
authors: Moo Ho
authors: MH
authors: Won
authors: Joon
authors: J
authors: Kim
authors: Sung-Woo
authors: SW
authors: Cho
authors: Tae-Cheon
authors: TC
authors: Kang
authors: Kyu Hyung
authors: KH
authors: Han
authors: Jinseu
authors: J
authors: Park
authors: Won Sik
authors: WS
authors: Eum
authors: Soo Young
authors: SY
authors: Choi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D021984:Cyclophilin A / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation / Q000188:drug therapy*; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis; D016328:NF-kappa B / Q000096:biosynthesis; D010447:Peptide Hydrolases / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D016328:NF-kappa B; D011993:Recombinant Fusion Proteins; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases; D010447:Peptide Hydrolases; C058973:peptidase-1 (Pleurodeles); D021984:Cyclophilin A; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate