title: Cell permeable NFAT inhibitory peptide Sim-2-VIVIT inhibits T-cell activation and alleviates allergic airway inflammation and hyper-responsiveness.
abstract: Nuclear factor of activated T cells (NFAT) is an important transcription factor for the production of interleukin (IL)-2 upon T-cell receptor (TcR) signaling. Therefore, inhibition of the NFAT-carcineurin pathway is an important target for inflammatory disease inhibition and graft rejection. A novel cell permeable peptide (CPP), Sim-2, has been identified from a human transcription factor, and Sim-2-CPP conjugated to β-galactosidase or EGFP protein was efficiently delivered into cells in vitro and in vivo. A cell permeable form of the NFAT inhibitory peptide VIVIT (Sim-2-VIVIT) was synthesized and showed inhibitory effects on human CD4 or CD8 T-cell activation through NFAT transcriptional activity suppression and IL-2 inhibition. Intranasal administration of the Sim-2-VIVIT peptide in an ovalbumin (OVA)-induced murine asthma model alleviated peribronchial and perivascular infiltration of inflammatory cells in the lung and caused airway remodeling and airway hyper-responsiveness. These results suggest that cell permeable Sim-2-VIVIT peptide has clinical potential as an immunosuppressive agent for inflammatory diseases.
authors.affiliation: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea. jeminchoi@hanyang.ac.kr
authors.forename: Je-Min
authors.initials: JM
authors.lastname: Choi
authors.forename: Jung-Ho
authors.initials: JH
authors.lastname: Sohn
authors.forename: Tae-Yoon
authors.initials: TY
authors.lastname: Park
authors.forename: Jung-Won
authors.initials: JW
authors.lastname: Park
authors.forename: Sang-Kyou
authors.initials: SK
authors.lastname: Lee
mesh_terms: D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors / Q000737:chemistry*; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D007376:Interleukin-2; D050778:NFATC Transcription Factors; D009842:Oligopeptides; C121611:VIVIT peptide