Which of the following is a calcineurium inhibitor -
Ans. is 'b' i.e., Cyclosporine o Cyclosporine inhibits transcription by binding to a protein called cyclophilin, This complex then inactivates calcineurin. (Calcineurin is a protein which is responsible for the transcription of cytokine gene)Mechanism of action of cyclosporineo Normally when antigen presenting cell (e.g. macrophage) present antigen to Helper Tcell, there is activation of T cell by sequantial intracellular events -First calcium ions, after binding to calmodulin activate a membrane serine / threonine phosphatase called calcineurin.Calcineurin activates nuclear factor of activated T cells (NFAT) by dephosphorylation.Activated NFAT migrates to nucleus and induce transcription of cytokines IL-2 and other cytokines.IL-2 activates T cells and cause proliferation of T cells.o Cyclosporine enters target cells and bind to cyclophilin (an immunophilin).o This cyctosporine-cyclophilin complex inactivates calcineurin -| IL-2 trascripitan and | proliferation of T cells.Mechanism of Nephrotoxicity caused bv cyclosporineo It is due to vasoconstriction of periglomerular afferent arterioles that decreases GFR.o It may lead to ARF or CRF.Mechanism of hypertension caused bv cyclosporineo Cyclosporine has some mineralocorticoids like action that causes fluid and salt retention - hypertension.
Cyclophoshamide
Cyclosporine
Etanercept
Sirolimus
Immunomodulator