Cell permeable NFAT inhibitory peptide Sim-2-VIVIT inhibits T-cell activation and alleviates allergic airway inflammation and hyper-responsiveness

Je Min Choi, Jung Ho Sohn, Tae Yoon Park, Jung Won Park, Sang Kyou Lee

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)170-176
Number of pages7
JournalImmunology Letters
Volume143
Issue number2
DOIs
Publication statusPublished - 2012 Apr 30

Fingerprint

Respiratory Hypersensitivity
NFATC Transcription Factors
Inflammation
T-Lymphocytes
Peptides
Interleukin-2
Transcription Factors
Galactosidases
Airway Remodeling
Intranasal Administration
Ovalbumin
Graft Rejection
Immunosuppressive Agents
T-Cell Antigen Receptor
Asthma
Lung

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

@article{f3aea6e61d2242fa8fec952218adf89b,
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.",
author = "Choi, {Je Min} and Sohn, {Jung Ho} and Park, {Tae Yoon} and Park, {Jung Won} and Lee, {Sang Kyou}",
year = "2012",
month = "4",
day = "30",
doi = "10.1016/j.imlet.2012.01.016",
language = "English",
volume = "143",
pages = "170--176",
journal = "Immunology Letters",
issn = "0165-2478",
publisher = "Elsevier",
number = "2",

}

Cell permeable NFAT inhibitory peptide Sim-2-VIVIT inhibits T-cell activation and alleviates allergic airway inflammation and hyper-responsiveness. / Choi, Je Min; Sohn, Jung Ho; Park, Tae Yoon; Park, Jung Won; Lee, Sang Kyou.

In: Immunology Letters, Vol. 143, No. 2, 30.04.2012, p. 170-176.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cell permeable NFAT inhibitory peptide Sim-2-VIVIT inhibits T-cell activation and alleviates allergic airway inflammation and hyper-responsiveness

AU - Choi, Je Min

AU - Sohn, Jung Ho

AU - Park, Tae Yoon

AU - Park, Jung Won

AU - Lee, Sang Kyou

PY - 2012/4/30

Y1 - 2012/4/30

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84862792153&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862792153&partnerID=8YFLogxK

U2 - 10.1016/j.imlet.2012.01.016

DO - 10.1016/j.imlet.2012.01.016

M3 - Article

C2 - 22342853

AN - SCOPUS:84862792153

VL - 143

SP - 170

EP - 176

JO - Immunology Letters

JF - Immunology Letters

SN - 0165-2478

IS - 2

ER -