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Toll-like receptor 3 contributes to inflammatory Schwann cell activation and Wallerian degeneration after peripheral nerve injury
말초신경 손상 후 슈반세포의 활성화와 Wallerian degeneration에서 톨유사수용체 3의 역할 규명

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Authors
백지연
Advisor
이성중
Major
자연과학대학 협동과정 유전공학전공
Issue Date
2014
Publisher
서울대학교 대학원
Keywords
toll-like receptorSchwann cellsWallerian degenerationSciatic nerve injurychemokinemacrophage infiltration
Description
학위논문 (석사)-- 서울대학교 대학원 : 협동과정 유전공학전공, 2014. 8. 이성중.
Abstract
It is well known that Schwann cells play an important role in Wallerian degeneration after peripheral nerve injury. Recently, it was reported that toll-like receptor (TLR) signaling contributes to Wallerian degeneration. Moreover, previous studies had found that TLR ligands-induced inflammatory Schwann cell is activated via TLR2 and 3. However, the role of TLR3 in Wallerian degeneration after peripheral nerve injury is still poorly understood. Hence, the objective of this study is to establish a clearer understanding of the role of TLR3 in Wallerian degeneration after a peripheral nerve injury. It was found that sciatic nerve crush injury reduced the number of degenerating myelin axons in TLR3 knock-out mice. After 7 days, TLR3 knock-out mice showed delayed sciatic nerve degeneration compared with WT mice. In addition, macrophage infiltration into injury site was significantly increased in WT mice, but not in TLR3 knock-out mice. The nerve injury-induced expression of macrophage infiltrated-related chemokines such as CC-chemokine ligand (CCL)2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β and CCL5/RANTES was compromised in Schwann cells of TLR3 knock-out mice in vitro and in vivo. Similarly, the TLR3 ligands- induced chemokine expression was reduced in Schwann cells derived from TLR3 KO mice. Finally, polyinosinic-polycytidylic acid (poly(I:C)), a synthetic TLR3 agonist, injection into the sciatic nerve of the rat induced macrophage infiltration in vivo. Taken together, these data show that TLR3 is required for the inflammatory Schwann cell activation and contributes to Wallerian degeneration after peripheral nerve injury.
Language
English
URI
http://hdl.handle.net/10371/131164
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College of Natural Sciences (자연과학대학)Program in Genetic Engineering (협동과정-유전공학전공)Theses (Master's Degree_협동과정-유전공학전공)
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