Editing Tacrolimus (section)

===Mechanism of action===
[[File:PDB 1fkk EBI.jpg|thumb|[[FKBP12]], the target protein of tacrolimus]]
Tacrolimus is a [[macrolide]] [[calcineurin inhibitor]]. In [[T cells]], activation of the T cell receptor normally increases intracellular calcium, which acts via [[calmodulin]] to activate [[calcineurin]]. Calcineurin then dephosphorylates the transcription factor [[NFAT|nuclear factor of activated T cells]] (NF-AT), which moves to the nucleus of the T cell and increases the activity of genes coding for IL-2 and related cytokines. Tacrolimus prevents the dephosphorylation of NF-AT.<ref>{{cite book| vauthors = Ganong WF |title= Review of medical physiology|edition=22nd |publisher=Lange medical books|page=530|isbn=978-0-07-144040-0|date= 8 March 2005}}</ref>

In detail, tacrolimus reduces [[Peptidylprolyl isomerase A|peptidylprolyl isomerase]] activity by binding to the immunophilin [[FKBP12]] (FK506 binding protein), creating a new complex. This FKBP12–FK506 complex interacts with and inhibits calcineurin, thus inhibiting both T [[lymphocyte]] signal transduction and IL-2 transcription.<ref name="Cell1991-Liu">{{cite journal | vauthors = Liu J, Farmer JD, Lane WS, Friedman J, Weissman I, Schreiber SL | title = Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes | journal = Cell | volume = 66 | issue = 4 | pages = 807–815 | date = August 1991 | pmid = 1715244 | doi = 10.1016/0092-8674(91)90124-H | s2cid = 22094672 }}</ref> Although this activity is similar to that of cyclosporin, the incidence of acute rejection is reduced by tacrolimus use over cyclosporin use.<ref name="Medscape2004-McCauley" /> Although short-term immunosuppression concerning patient and graft survival is found to be similar between the two drugs, tacrolimus results in a more favorable lipid profile, and this may have important long-term implications given the prognostic influence of rejection on graft survival.<ref>{{cite journal | vauthors = Abou-Jaoude MM, Najm R, Shaheen J, Nawfal N, Abboud S, Alhabash M, Darwish M, Mulhem A, Ojjeh A, Almawi WY | title = Tacrolimus (FK506) versus cyclosporine microemulsion (neoral) as maintenance immunosuppression therapy in kidney transplant recipients | journal = Transplantation Proceedings | volume = 37 | issue = 7 | pages = 3025–3028 | date = September 2005 | pmid = 16213293 | doi = 10.1016/j.transproceed.2005.08.040 }}</ref>