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.

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.

• Authors: Dean Wu, Yuan-Chii G Lee, Hsing-Cheng Liu, Rey-Yue Yuan, Hung-Yi Chiou, Chia-Hsiu Hung, Chaur-Jong Hu
• Journal: Clinical biochemistry (Clin Biochem) Vol. 46 Issue 12 Pg. 1058-1064 (Aug 2013) ISSN: 1873-2933 [Electronic] United States
• PMID: 23726813 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Chemical References

• Toll-Like Receptors
• Ubiquitin

Topics

• Brain Ischemia (genetics, pathology)
• Case-Control Studies
• Gene Expression Profiling
• Gene Expression Regulation
• Humans
• Proteolysis
• Reproducibility of Results
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (genetics)
• Stroke (genetics, pathology)
• Toll-Like Receptors (genetics, metabolism)
• Ubiquitin (metabolism)