The nuclear factor of activated T cells (NFAT) is a family of transcription factors that regulate immune responses and adaptive response in skeletal and cardiac muscle. NFAT inhibitor (VIVIT peptide) is a cell-permeable peptide that selectively inhibits calcineurin-mediated dephosphorylation of NFAT[1]. In peripheral blood CD14+ monocytes isolated from rheumatoid arthritis patients, treatment with 10μM of NFAT inhibitor plus 100ng/mL of recombinant human RANKL and 50ng/mL of M‐CSF for 24h significantly inhibited nuclear translocation of NFATc1, but not that of peroxisome proliferator-activated receptor γ coactivator 1β. Long-term (21 days) treatment with NFAT inhibitor in combination with M‐CSF and RANKL significantly inhibited the cytoplasmic levels of cathepsin K, tartrate‐resistant acid phosphatase, and matrix metalloproteinase 9[2]. Intraperitoneal administration of NFAT (10mg/kg) once daily for 2 days prevented T-cell activation and proliferation in C3H/HeN mice[3].
作用机制
NFAT inhibitor potently and selectively inhibits the NFAT-calcineurin interaction without affecting calcineurin phosphatase activity. It was developed based on the conserved calcineurin docking site of NFAT[1].
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