CAJ | 학술논문

背景:AG490是新近发现的一种JAK激酶抑制剂,可以和受体酪氨酸激酶竞争结合位点,从而通过阻断JAK/STAT通路达到抑制γ-干扰素等器官移植排斥反应相关细胞因子活化,进而抑制器官抑制排斥反应.目的:验证AG490作为免疫抑制剂的可能性及其基本作用途径,并与环孢素A及他克莫司相比较. 设计、时间及地点:对照观察,于2007-10/2008-04在福建省协和医院泌尿外科研究所完成.材料:AG490购自美国SIGMA公司.方法:取8位健康成年人外周静脉血,密度梯度法分离淋巴细胞,分别应用植物血凝素、白细胞介素2、淋巴细胞混合培养诱导人淋巴细胞产生增殖. 主要观察指标:分别采用酶联免疫吸附法检测在AG490、环孢素A、他克莫司作用下人淋巴细胞(T,B混合存在)增殖过程中细胞因子白细胞介素2、白细胞介素6、γ-干扰素的质量浓度.结果:在体外实验中,AG490对于植物血凝素、白细胞介素2刺激及淋巴细胞混合培养引起的人淋巴细胞增殖反应中白细胞介素2、γ-干扰素的分泌可以起到抑制作用(P < 0.05),但对于白细胞介素6分泌无抑制作用(P < 0.05),此作用与临床常用免疫抑制剂环孢素A、他克莫司相类似.结论:AG490有可能是一种潜在的免疫抑制剂.
배경:AG490시신근발현적일충JAK격매억제제,가이화수체락안산격매경쟁결합위점,종이통과조단JAK/STAT통로체도억제γ-간우소등기관이식배척반응상관세포인자활화,진이억제기관억제배척반응.목적:험증AG490작위면역억제제적가능성급기기본작용도경,병여배포소A급타극막사상비교. 설계、시간급지점:대조관찰,우2007-10/2008-04재복건성협화의원비뇨외과연구소완성.재료:AG490구자미국SIGMA공사.방법:취8위건강성년인외주정맥혈,밀도제도법분리림파세포,분별응용식물혈응소、백세포개소2、림파세포혼합배양유도인림파세포산생증식. 주요관찰지표:분별채용매련면역흡부법검측재AG490、배포소A、타극막사작용하인림파세포(T,B혼합존재)증식과정중세포인자백세포개소2、백세포개소6、γ-간우소적질량농도.결과:재체외실험중,AG490대우식물혈응소、백세포개소2자격급림파세포혼합배양인기적인림파세포증식반응중백세포개소2、γ-간우소적분비가이기도억제작용(P < 0.05),단대우백세포개소6분비무억제작용(P < 0.05),차작용여림상상용면역억제제배포소A、타극막사상유사.결론:AG490유가능시일충잠재적면역억제제.
BACKGROUND: AG490 is a newly found JAK kinase inhibitor, which can compete with receptor tyrosine kinase for binding site to block JAK/STAT pathway, inhibit rejection-related cytokine activation such as interferon-gamma (IFN-γ) ultimately inhibiting rejection.OBJECTIVE: To evaluate the possibility and prospect of the AG490 as a potential immunosuppressor, explore its basic mechanism in comparison with Cyclosporine A (CsA).DESIGN, TIME AND SETTING: Comparative observation was performed at the Institute of Urinary Surgery, Fujian Union Hospital from October 2007 to April 2008.MATERIALS: AG490 was purchased from Sigma, USA.METHODS: Human peripheral blood lymphocyte (both T and B) were harvested from 8 healthy donors. Lymphocyte were isolated by density gradient method and cultured with phytohemagglutinin, interleukin-2 (IL-2) or mixed lymphocyte culture to induce human lymphocyte proliferation. MAIN OUTCOME MEASURES: ELISA was used to detect the concentration of IL-2, IFN-γ and IL-6 in different culture systems with the tyrphostin (AG490), CsA or FK506. RESULTS: IL-2 and IFN-γ in culture systems of phytohemagglutinin, IL-2 or mixed lymphocyte culture were inhibited by AG490 (P < 0.05), but IL-6 was not suppressed by AG490 (P < 0.05). This effect was similar to clinical CsA or FK506. CONCLUSION: AG490 may be a potential immunosuppressor.