货号：T5684

储存条件：粉末-20°C可保存3年；液体-80°C可保存12月。

产品描述

The immunophilin FKBP12 is one of the most abundant and conserved proteins in biology. It is the primary receptor for the immunosuppressant actions of ascomycin in whose presence FKBP12 binds to and inhibits CaN, disrupting IL formation in lymphocytes. Tacrolimus(FK-506) block early events in T lymphocyte activation by its immunosuppressive effects such as phosphoinositide turnover, reducing peptidyl-prolyl isomerase activity in T cells by binding to the FKBP12 which will create a new complex. FK-506 inhibited FKBP12 for activity with IC50 of 3nM. Furthermore, FK-506 Inhibited secretion of IL-1, IL-2 (IC50 = 1 nM), IL-3, IL-4, IL-6 (IC50 = 35 nM), GM-CSF, TNFα (IC50 = 10 nM), IFNγ and Myc from activated T cells. In terms of anti-inflammatory activity in rat RBL2H3 cells, the inhibition of FK506 to DNP-BSA-induced TNF-alpha production pre-incubated for 15 mins with IC50 of 0.25 nM. FK-506 can decrease the serum nitrate and thiobarbituric acid reactive substance (TBARS) levels along with reduction in tissue myeloperoxidase (MPO) and total calcium levels. FK-506 ameliorates the increase in the neuronal edema and axonal degeneration in rats with ischemia reperfusion (I/R) . In the presence of 10ng/mL FK-506, nuclear extracts from Jurkat cells that had been stimulated for 2 hours with PMA and ionomycin transcribe the IL-2 G-less template in amounts nearly equivalent to extracts from fully stimulated Jurkat cells . Overexpression of FKBP12 by transfection enhanced the ability of FK-506 to inhibit calcineurin phosphatase activity with IC50 of 2nM, compared with cells transfected with the expression vector alone (IC50 > 30 nM). The IC50 value for FK-506 inhibition of IgE activation-induced transcripts for TNF-α decreased from 40nM to 10nM in FKBP12 transfectants. Similarly, the IC50 value for inhibition of IL-6 transcripts decreased from > 1000 nM to 35 nM, suggesting FKBP12 is the dominant cytosolic protein that mediates FK506 inhibition of TNF-α and IL-6 transcripts.

作用机制

FK506 selectively inhibits the enzymatic activity of the calcium/calmodulin-dependent protein phosphatase CaN.

产品信息