Gabryel Bozena, Łabuzek Krzysztof, Małecki Andrzej, Herman Zbigniew S
Department of Pharmacology, Medical University of Silesia, Medyków 18, PL 40-752 Katowice, Poland.
Pol J Pharmacol. 2004 Jan-Feb;56(1):129-36.
The aim of present study was to evaluate the effects of immunophilin ligands (cyclosporin A, FK506 and rapamycin) on the simulated ischemia-induced release of pro-inflammatory cytokines (IL-1beta, TNF-alpha and IL-2) in rat primary astrocyte cell cultures. Astrocytes were exposed to cyclosporin A (CsA) (0.25, 0.5, 1, 10, 20 and 50 microM), FK506 (1, 10, 100, 1000 nM) and rapamycin (10, 100, 500 and 1000 nM). In vitro simulated ischemia significantly increased secretion of IL-1beta, TNF-alpha and IL-2 by astrocyte cultures deprived of microglia (by shaking and incubating with L-leucine methyl ester). CsA (at concentrations of 10-50 microM), FK506 (at all used concentrations) and rapamycin (in dose-dependent manner) significantly attenuated IL-1beta release after 24 h exposure to ischemic conditions. Immunophilin ligands at all used concentrations significantly decreased TNF-alpha levels in culture media after 24 h exposure to ischemia. Moreover, significant decrease in IL-2 secretion at 0.25, 0.5, 1 and 50 microM CsA and FK506 at concentrations of 100 and 1000 nM were observed. The results suggest that immunophilin ligands may regulate glial activity during ischemia by affecting the release of pro-inflammatory cytokines.
本研究的目的是评估免疫亲和素配体（环孢素A、FK506和雷帕霉素）对大鼠原代星形胶质细胞培养物中模拟缺血诱导的促炎细胞因子（IL-1β、TNF-α和IL-2）释放的影响。将星形胶质细胞暴露于环孢素A（CsA）（0.25、0.5、1、10、20和50微摩尔）、FK506（1、10、100、1000纳摩尔）和雷帕霉素（10、100、500和1000纳摩尔）。体外模拟缺血显著增加了去除小胶质细胞（通过振荡并与L-亮氨酸甲酯孵育）的星形胶质细胞培养物中IL-1β、TNF-α和IL-2的分泌。CsA（浓度为10 - 50微摩尔）、FK506（所有使用浓度）和雷帕霉素（呈剂量依赖性）在暴露于缺血条件24小时后显著减弱了IL-1β的释放。在暴露于缺血24小时后，所有使用浓度的免疫亲和素配体均显著降低了培养基中TNF-α的水平。此外，观察到0.25、0.5、1和50微摩尔的CsA以及100和1000纳摩尔浓度的FK506使IL-2分泌显著减少。结果表明，免疫亲和素配体可能通过影响促炎细胞因子的释放来调节缺血期间的神经胶质细胞活性。
