title: Transduced PEP-1-FK506BP inhibits the inflammatory response in the Raw 264.7 cell and mouse models.
abstract: FK506 binding protein 12 (FK506BP) is an immunophilin that acts as a receptor for the immunosuppressant drug FK506. Although the precise action of FK506BP remains unclear, it has emerged as a potential drug target for several inflammatory diseases. This study investigated the protective effects of FK506BP on inflammation in vitro and in vivo using protein transduction. A cell-permeable expression vector PEP-1-FK506BP was constructed. Lipopolysaccharide (LPS)- or 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated Raw 264.7 cells and ICR mice were treated with PEP-1-FK506BP. The expression of inflammatory response enzymes and cytokines was analyzed by Western blot, reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and electrophoretic mobility shift assay. PEP-1-FK506BP efficiently transduced into Raw 264.7 cells and markedly inhibited the expression levels of cyclooxygenase-2 as well as pro-inflammatory cytokines. Furthermore, transduced PEP-1-FK506BP significantly reduced activation of nuclear factor-kappa B (NF-κB) and phosphorylation of p38 mitogen-activated protein kinase (MAPK) in the cells, whereas PEP-1-FK506BP reduced phosphorylation of p38 and extracellular signal-regulated kinase (ERK) in the animal models. These results indicate that PEP-1-FK506BP inhibits inflammatory response cytokines and enzymes by blocking NF-κB and MAPK including the phosphorylation of p38 and/or ERK MAPK in vitro and in vivo, suggesting that PEP-1-FK506BP may be a therapeutic agent against inflammatory skin diseases.
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon, Republic of Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Hoon Jae
authors.initials: HJ
authors.lastname: Jeong
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.forename: Mi Jin
authors.initials: MJ
authors.lastname: Kim
authors.forename: Jae Jin
authors.initials: JJ
authors.lastname: An
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Sohn
authors.forename: Hye Won
authors.initials: HW
authors.lastname: Kang
authors.forename: Min Jea
authors.initials: MJ
authors.lastname: Shin
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Ahn
authors.forename: Soon Won
authors.initials: SW
authors.lastname: Kwon
authors.forename: Duk-Soo
authors.initials: DS
authors.lastname: Kim
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Cho
authors.forename: Jinseu
authors.initials: J
authors.lastname: Park
authors.forename: Won Sik
authors.initials: WS
authors.lastname: Eum
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
mesh_terms: D000818:Animals; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007249:Inflammation; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D023421:Models, Animal; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D012871:Skin Diseases / Q000188:drug therapy* / Q000276:immunology; D016559:Tacrolimus / Q000627:therapeutic use*; D022021:Tacrolimus Binding Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014161:Transduction, Genetic
chemical_list: D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D016328:NF-kappa B; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D022021:Tacrolimus Binding Proteins; D016559:Tacrolimus