Dean Wu1, Yuan-Chii G Lee2, Hsing-Cheng Liu3, Rey-Yue Yuan4, Hung-Yi Chiou5, Chia-Hsiu Hung6, Chaur-Jong Hu7. 1. Department of Neurology, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan. 2. Graduate Institute of Biomedical Informatics, Taipei Medical University, Taipei, Taiwan. 3. Department of Psychosomatic Medicine, Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan; Department of Psychiatry, School of Medicine, Taipei Medical University, Taipei, Taiwan. 4. Department of Neurology, Taipei Medical University, Taipei, Taiwan. 5. Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan; School of Public Health, Taipei Medical University, Taipei, Taiwan. 6. Department of Pediatrics, Taipei Medical University Wan Fang Hospital, Taipei, Taiwan. 7. 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.
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. 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.
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 strokepatients and 12 controls were selected from among 89 ischemic strokepatients 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 strokepatients 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.