title: Identification of TLR downstream pathways in stroke patients.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Neurology, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Dean
authors.initials: D
authors.lastname: Wu
authors.affiliation: Graduate Institute of Biomedical Informatics, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yuan-Chii G
authors.initials: YG
authors.lastname: Lee
authors.affiliation: Department of Psychosomatic Medicine, Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan; Department of Psychiatry, School of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Hsing-Cheng
authors.initials: HC
authors.lastname: Liu
authors.affiliation: Department of Neurology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Rey-Yue
authors.initials: RY
authors.lastname: Yuan
authors.affiliation: Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan; School of Public Health, Taipei Medical University, Taipei, Taiwan.
authors.forename: Hung-Yi
authors.initials: HY
authors.lastname: Chiou
authors.affiliation: Department of Pediatrics, Taipei Medical University Wan Fang Hospital, Taipei, Taiwan.
authors.forename: Chia-Hsiu
authors.initials: CH
authors.lastname: Hung
authors.affiliation: Department of Neurology, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; Department of Neurology, Taipei Medical University, Taipei, Taiwan; Department of Neurology, National Defense University, Taipei, Taiwan. Electronic address: chaurjongh@yahoo.com.tw.
authors.forename: Chaur-Jong
authors.initials: CJ
authors.lastname: Hu
mesh_terms: D002545:Brain Ischemia / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D059748:Proteolysis; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D020521:Stroke / Q000235:genetics* / Q000473:pathology; D051193:Toll-Like Receptors / Q000235:genetics* / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D051193:Toll-Like Receptors; D025801:Ubiquitin
keywords: Ischemic stroke; Pathway analysis; Toll-like receptors; mRNA