Synergistic Effects of Calcineurin Inhibitors and Steroids on Steroid Sensitivity of Peripheral Blood Mononuclear Cells.
Synergistic Effects of Calcineurin Inhibitors and Steroids on Steroid Sensitivity of Peripheral Blood Mononuclear Cells.
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钙调神经磷酸酶抑制剂和类固醇对外周血单核细胞类固醇敏感性的协同作用。
DOI：
10.3727/215517914x681802
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
M. Shimazu
中科院分区：
文献类型：
--
作者：
H. Takeuchi;H. Iwamoto;Yuki Nakamura;T. Hirano;O. Konno;Y. Kihara;N. Chiba;T. Yokoyama;K. Takano;T. Toraishi;K. Okuyama;Chie Ikeda;Sachiko Tanaka;K. Onda;A. Soga;Yukiko Kikuchi;T. Kawaguchi;S. Kawachi;S. Unezaki;M. Shimazu
类固醇受体（SR）复合物含有FKBP 51和FKBP 52，它们与他克莫司（TAC）和亲环素40结合，后者又与环孢菌素（CYA）结合;这些影响类固醇-SR复合物的核内移动性。认为类固醇和钙调磷酸酶抑制剂（CNI）对SR复合物存在药效学相互作用。我们研究了CNIs对类固醇敏感性的影响。甲基强的松龙（MPSL）敏感性估计为抑制50%的外周血单个核细胞有丝分裂的浓度（IC 50）和MPSL浓度-增殖抑制率曲线下面积（CPS-AUC）在30名健康受试者。MPSL敏感性在加和组（AG）和混合培养组（MCG）之间进行比较，加和组（AG）作为MPSL敏感性，其是CNIs的增殖抑制率加到MPSL的增殖抑制率的结果，混合培养组（MCG）作为MPSL和CNIs两者在相同患者中的混合培养的MPSL敏感性。对23例肾移植受者在CNI给药前和给药后2个月测定MPSL和皮质醇敏感性的IC 50值。MCG中MPSL的IC 50和CPS-AUC值低于给予TAC和CYA的AG。TAC组MCG和AG的CPS-AUC比值较低。TAC和CYA给药后MPSL和皮质醇的IC 50值有降低的趋势，TAC给药后皮质醇的IC 50值有显著差异。TAC和CYA均增加类固醇敏感性。此外，TAC对增加敏感性有更大的作用。因此，CNI和类固醇的伴随施用可增加类固醇敏感性。
The steroid receptor (SR) complex contains FKBP51 and FKBP52, which bind to tacrolimus (TAC) and cyclophilin 40, which, in turn, bind to cyclosporine (CYA); these influence the intranuclear mobility of steroid-SR complexes. Pharmacodynamic interactions are thought to exist between steroids and calcineurin inhibitors (CNIs) on the SR complex. We examined the effect of CNIs on steroid sensitivity. Methylprednisolone (MPSL) sensitivity was estimated as the concentration inhibiting mitosis in 50% (IC50) of peripheral blood mononuclear cells and as the area under the MPSL concentration-proliferation suppressive rate curves (CPS-AUC) in 30 healthy subjects. MPSL sensitivity was compared between the additive group (AG) as the MPSL sensitivity that was a result of addition of the proliferation suppressive rate of CNIs to that of MPSL and the mixed culture group (MCG) as MPSL sensitivity of mixed culture with both MPSL and CNIs in identical patients. IC50 values of MPSL and cortisol sensitivity were examined before and 2 months after CNI administration in 23 renal transplant recipients. IC50 and CPS-AUC values of MPSL were lower in the MCG than in the AG with administration of TAC and CYA. The CPS-AUC ratio of MCG and AG was lower in the TAC group. IC50 values of MPSL and cortisol tended to be lower after administration of TAC and CYA, and a significant difference was observed in the IC50 of cortisol after TAC administration. Steroid sensitivity increased with both TAC and CYA. Furthermore, TAC had a greater effect on increasing sensitivity. Thus, concomitant administration of CNIs and steroids can increase steroid sensitivity.
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影响因子：
2.9
作者：
Banerjee, Ananya;Periyasamy, Sumudra;Wolf, Irene M.;Hinds, Terry D., Jr.;Yong, Weidong;Shou, Weinian;Sanchez, Edwin R.
通讯作者：
Sanchez, Edwin R.
影响因子：
14.8
作者：
Alagramam KN;Gopal SR;Geng R;Chen DH;Nemet I;Lee R;Tian G;Miyagi M;Malagu KF;Lock CJ;Esmieu WR;Owens AP;Lindsay NA;Ouwehand K;Albertus F;Fischer DF;Bürli RW;MacLeod AM;Harte WE;Palczewski K;Imanishi Y
通讯作者：
Imanishi Y
影响因子：
2.9
作者：
Davies, TH;Ning, YM;Sánchez, ER
通讯作者：
Sánchez, ER
松鼠猴亲免素 FKBP51 是糖皮质激素受体结合的有效抑制剂。
影响因子：
4.8
作者：
Denny,WB;Valentine,DL;Reynolds,PD;Smith,DF;Scammell,JG
通讯作者：
Scammell,JG