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.
References
Citations
Related Concepts
Related Feeds
Asthma
This feed focuses in Asthma in which your airways narrow and swell. This can make breathing difficult and trigger coughing, wheezing and shortness of breath.
Allergy and Asthma
Allergy and asthma are inflammatory disorders that are triggered by the activation of an allergen-specific regulatory t cell. These t cells become activated when allergens are recognized by allergen-presenting cells. Here is the latest research on allergy and asthma.
Basement Membranes
Basement membranes are thin, specialized extracellular matrices surrounding most tissues in all metazoans. Here is the latest research on basement membranes.