TLR激动剂抑制IL-27诱导的THP-1细胞HLA-DR的表达  

TLR Agonists Inhibit IL-27-Induced HLA-DR Expression in THP-1 Cells

作　　者：冯晓明[1] 刘娜[1] 陈晓梨[1] 胡丽燕[1] 杨少光[1] 卢士红[1] 韩忠朝[1] 

机构地区：[1]中国医学科学院中国协和医科大学血液学研究所实验血液学国家重点实验室,天津市300020

出　　处：《医学分子生物学杂志》2008年第3期194-200,共7页Journal of Medical Molecular Biology

基　　金：国家自然科学基金(No.30570357;30600238);天津市科学技术委员会项目(No.06YFSZSF01300;05YFJZJC01500)~~

摘　　要：目的研究白介素27(IL-27)对THP-1单核细胞系Ⅱ类转录活化子(classⅡtransactivator,CⅡTA)和Ⅱ类主要组织相容性复合物(major histocom patibility complex classⅡ,MHCⅡ)分子的表达的影响及Toll样受体(Toll-likereceptor,TLR)激动剂LPS和Pam3CSK4的干预作用。方法RT-PCR检测CⅡTAⅠ、Ⅲ和Ⅳ以及人白细胞抗原(human leukocyte antigen,HLA)-DRA和干扰素调节因子-1(interferon regulatory factor-1,IRF-1)mRNA的表达。半定量PCR检测HLA-DRA、DRB、DPA、DPB、DQA、DQB、IRF-1、CⅡTA mRNA的表达。流式细胞术检测细胞表面HLA-DR的表达。结果IL-27刺激24h后可分别上调THP-1细胞CⅡTAⅢ、CⅡTAⅣ和IRF-1mRNA表达水平。IL-27刺激24h和48h可升高MHCⅡ类分子mRNA的表达,并能诱导HLA-DR在28%和53%的THP-1细胞表面表达。在THP-1细胞和PMA诱导的THP-1巨噬细胞,LPS和Pam3CSK4均可抑制IL-27诱导的CⅡTA和HLA-DR的表达。结论IL-27可上调THP-1细胞CⅡTA和MHCⅡ类分子的表达,这种作用可被LPS和Pam3CSK4抑制。Objective To investigate the effect of interleukin-27 （IL-27） on the expression of class Ⅱ transactivator （CIITA） and major histocompatibility complex class Ⅱ （MHC Ⅱ） genes in THP-1 cells and the intervention by Toll-like receptor （ TLR ） agonists LPS and Pam3CSK4. Methods Real-time PCR was performed to examine the mRNA expression levels of CI- ITA Ⅰ , Ⅲ and Ⅳ, human leukocyte antigen （HLA） -DRA and interferon regulatory factor-1 （IRF-1） . Semi-quantitative RT-PCR was performed to assess the mRNA levels of HLA-DRA, DRB, DPA, DPB, DQA, DQB, IRF-1 and CIITA. Flow cytometry was used to determine the surface expression of HLA-DR molecules. Results After 24 hours of stimulation, IL-27 increased the CIITA m, CIITAIV and IRF-1 mRNA levels 14-, 38- and 8-folds respectively. IL-27 increased MHC II mRNA levels and induced surface expression of HLA-DR in 28% and 53% of THP-1 cells after 24-hour and 48-hour of incubation. In both THP-1 cells and PMA-activated THP-1 macrophages, LPS and Pam3CSK4 inhibited IL-27 inducible CIITA and MHC Ⅱ expression. Conclusion IL- 27 could increase CIITA and MHC Ⅱ expression in THP-1 cells, and these effects could be inhibited by TLR2 and TLR4 agonists.

关 键 词：白介素27 THP-1细胞 Ⅱ类转录活化子 Ⅱ类主要组织相容性复合体 Toll样受体激动剂 

分 类 号：Q813[生物学—生物工程]