Identification of TLR downstream pathways in stroke patients

被引:47
作者
Wu, Dean [1 ,2 ]
Lee, Yuan-Chii G. [3 ]
Liu, Hsing-Cheng [4 ,5 ]
Yuan, Rey-Yue [6 ]
Chiou, Hung-Yi [2 ,7 ]
Hung, Chia-Hsiu [8 ]
Hu, Chaur-Jong [1 ,6 ,9 ]
机构
[1] Taipei Med Univ, Shuang Ho Hosp, Dept Neurol, New Taipei City, Taiwan
[2] Taipei Med Univ, Grad Inst Clin Med, Taipei, Taiwan
[3] Taipei Med Univ, Grad Inst Biomed Informat, Taipei, Taiwan
[4] Taipei City Hosp, Dept Psychosomat Med, Taipei City Psychiat Ctr, Taipei, Taiwan
[5] Taipei Med Univ, Dept Psychiat, Sch Med, Taipei, Taiwan
[6] Taipei Med Univ, Dept Neurol, Taipei, Taiwan
[7] Taipei Med Univ, Sch Publ Hlth, Taipei, Taiwan
[8] Taipei Med Univ, Dept Pediat, Wan Fang Hosp, Taipei, Taiwan
[9] Natl Def Univ, Dept Neurol, Taipei, Taiwan
关键词
Toll-like receptors; Ischemic stroke; mRNA; Pathway analysis; TOLL-LIKE RECEPTORS; INNATE; ATHEROSCLEROSIS; INTEGRATION; EXPRESSION; MURINE; FAMILY; TRAF6; KEGG;
D O I
10.1016/j.clinbiochem.2013.05.059
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
100118 [医学信息学]; 100208 [临床检验诊断学];
摘要
Objective: Toll-like receptors (TLRs) are important molecules for detecting both pathogen invasion and tissue damage. The expression of TLR4 is upregulated in ischemic stroke, at least in the subacute stage. However, the TLR downstream pathways in the context of stroke have not been well studied in previous research. The purpose of this study is to elucidate the TLR4 downstream pathways following ischemic stroke. Design and methods: In this study, 12 ischemic stroke patients and 12 controls were selected from among 89 ischemic stroke patients and 166 controls. The chosen subjects had the highest levels of TLR4 mRNA in the peripheral blood. The differences in the TLR downstream signaling pathways, which were studied by using an RT2 Profiler TM PCR array system (Qiagen), were analyzed. The differentially expressed genes were analyzed by using GeneSpring GX and visualized based on the TLR pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results: The genes upregulated in stroke patients were found to be involved in the MyD88-independent pathway and in UBE2V1-TRAF6 ubiquitin-mediated proteolysis. The genes were more expressed in extracellular space, receptor binding, and cytokine receptor binding by use of gene ontology (GO) terms than in control patients. Conclusions: We found that the MyD88-independent pathway and the ubiquitin-mediated proteolysis pathway, especially TRAF6, may be the most vital molecules among TLR downstream pathways in incidences of ischemic stroke. (C) 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
引用
收藏
页码:1058 / 1064
页数:7
相关论文
共 30 条
[1]
Toll-like receptors on the fork roads between innate and adaptive immunity [J].
Abdelsadik, Ahmed ;
Trad, Ahmad .
HUMAN IMMUNOLOGY, 2011, 72 (12) :1188-1193
[2]
Toll-like receptors: critical proteins linking innate and acquired immunity [J].
Akira, S ;
Takeda, K ;
Kaisho, T .
NATURE IMMUNOLOGY, 2001, 2 (08) :675-680
[3]
[Anonymous], J EXP CLIN MED
[4]
Downstream Toll-like receptor signaling mediates adaptor-specific cytokine expression following focal cerebral ischemia [J].
Bolanle, Famakin ;
Yongshan, Mou ;
Maria, Spatz ;
Modinat, Lawal ;
Hallenbeck, John .
JOURNAL OF NEUROINFLAMMATION, 2012, 9
[5]
Bradley WG., 2004, Neurology in clinical practice, V4th
[6]
Toll-like receptors 2 and 4 in ischemic stroke: outcome and therapeutic values [J].
Brea, David ;
Blanco, Miguel ;
Ramos-Cabrer, Pedro ;
Moldes, Octavio ;
Arias, Susana ;
Perez-Mato, Maria ;
Leira, Rogelio ;
Sobrino, Tomas ;
Castillo, Jose .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2011, 31 (06) :1424-1431
[7]
Toll-like receptor 4 is involved in brain damage and inflammation after experimental stroke [J].
Caso, Javier R. ;
Pradillo, Jesus M. ;
Hurtado, Olivia ;
Lorenzo, Pedro ;
Moro, Maria A. ;
Lizasoain, Ignacio .
CIRCULATION, 2007, 115 (12) :1599-1608
[8]
The toll of toll-like receptors, especially toll-like receptor 2, on murine atherosclerosis [J].
Curtiss, L. K. ;
Tobias, P. S. .
CURRENT DRUG TARGETS, 2007, 8 (12) :1230-1238
[9]
Dean W, 2012, CLIN BIOCHEM, V45, P1316
[10]
Activation of the IκB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain [J].
Deng, L ;
Wang, C ;
Spencer, E ;
Yang, LY ;
Braun, A ;
You, JX ;
Slaughter, C ;
Pickart, C ;
Chen, ZJ .
CELL, 2000, 103 (02) :351-361