What do calcineurin inhibitors do?
What do calcineurin inhibitors do?
Calcineurin inhibitors are immunosuppressants used to manage autoimmune conditions including but not limited to lupus nephritis, idiopathic inflammatory myositis, interstitial lung disease, atopic dermatitis, and many more. In addition, they are used as mainstays for immunosuppression in solid organ transplants.
How does calcineurin activate NFAT?
Signaling by the B cell receptor and the T cell receptor stimulate transcription by NFAT factors via calcium (reviewed in Gwack et al. 2007). Cytosolic calcium from intracellular stores and extracellular sources binds calmodulin and activates the protein phosphatase calcineurin.
What is the consequence of calcineurin inactivation?
Calcineurin inactivation leads to decreased responsiveness to LPS in macrophages and dendritic cells and protects against LPS-induced toxicity in vivo. Innate Immun.
Is calcineurin a transcription factor?
Calcineurin is a conserved Ca2+/calmodulin-specific serine-threonine protein phosphatase that mediates many Ca2+-dependent signaling events. In yeast, calcineurin dephosphorylates Crz1p, a transcription factor that binds to the calcineurin-dependent response element, a 24-bp promoter element.
What is calcineurin NFAT?
The calcineurin-NFAT pathway regulates gene expression in response to changes in intracellular calcium concentration and plays important roles in many tissues, including lymphocytes, neurons, and myocytes.
What is the role of NFAT?
Nuclear factor of activated T-cells (NFAT) is a family of transcription factors shown to be important in immune response. One or more members of the NFAT family is expressed in most cells of the immune system. NFAT is also involved in the development of cardiac, skeletal muscle, and nervous systems.
What is the mechanism of action of tacrolimus?
Tacrolimus acts by reducing peptidyl-prolyl isomerase activity by binding to the immunophilin FKBP-12 (FK506 binding protein) creating a new complex. This inhibits both T-lymphocyte signal transduction and IL-2 transcription.
