title: Transduced PEP-1-FK506BP ameliorates atopic dermatitis in NC/Nga mice.
abstract: Immunophilin, FK506-binding protein 12 (FK506BP), is a receptor protein for the immunosuppressive drug FK506 by the FK506BP/FK506 complex. However, the precise function of FK506BP in inflammatory diseases remains unclear. Therefore, we examined the protective effects of FK506BP on atopic dermatitis (AD) in tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ)-induced HaCaT cells and 2,4-dinitrofluorobenzene-induced AD-like dermatitis in Nishiki-nezumi Cinnamon/Nagoya (NC/Nga) mice using a cell-permeable PEP-1-FK506BP. Transduced PEP-1-FK506BP significantly inhibited the expression of cytokines, as well as the activation of NF-κB and mitogen-activated protein kinase (MAPK) in TNF-α/IFN-γ-induced HaCaT cells. Furthermore, topical application of PEP-1-FK506BP to NC/Nga mice markedly inhibited AD-like dermatitis as determined by a histological examination and assessment of serum IgE levels, as well as cytokines and chemokines. These results indicate that PEP-1-FK506BP inhibits NF-κB and MAPK activation in cells and AD-like skin lesions by reducing the expression levels of cytokines and chemokines, thus suggesting that PEP-1-FK506BP may be a potential therapeutic agent for AD.
authors: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon, Korea.
authors: So Young
authors: SY
authors: Kim
authors: Eun Jeong
authors: EJ
authors: Sohn
authors: Dae Won
authors: DW
authors: Kim
authors: Hoon Jae
authors: HJ
authors: Jeong
authors: Mi Jin
authors: MJ
authors: Kim
authors: Hye Won
authors: HW
authors: Kang
authors: Min Jea
authors: MJ
authors: Shin
authors: Eun Hee
authors: EH
authors: Ahn
authors: Soon Won
authors: SW
authors: Kwon
authors: Young Nam
authors: YN
authors: Kim
authors: Hyung Joo
authors: HJ
authors: Kwon
authors: Tae-Yoon
authors: TY
authors: Kim
authors: Kil Soo
authors: KS
authors: Lee
authors: Jinseu
authors: J
authors: Park
authors: Won Sik
authors: WS
authors: Eum
authors: Soo Young
authors: SY
authors: Choi
mesh_terms: D000818:Animals; D003543:Cysteamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000235:genetics; D020935:MAP Kinase Signaling System; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000502:physiology / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000502:physiology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics
chemical_list: D016328:NF-kappa B; C503924:Pep-1 peptide; D010455:Peptides; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D007073:Immunoglobulin E; D003543:Cysteamine; D007371:Interferon-gamma; D022021:Tacrolimus Binding Proteins