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.
Bibliographical noteFunding Information:
This work was supported by National Creative Research Initiatives , a grant from the National Research Foundation of Korea funded by the Korean Government grant ( 2011-0000425 ) to S.K.L. and the Brain Korea 21 (BK21) Program. This work was also supported by a grant from the Basic Science Research Program through the National Research Foundation of Korea grants ( 2011-0026447 and 2011-0012859 ) to J.M.C.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy