title: Toll-Like Receptor 3 Contributes to Wallerian Degeneration after Peripheral Nerve Injury.
abstract: It is well known that Schwann cells play an important role in Wallerian degeneration after peripheral nerve injury. Previously, we reported that toll-like receptor 3 (TLR3) is expressed on Schwann cells, implicating its role in Schwann cell activation during Wallerian degeneration. In this study, we tested this possibility using TLR3 knock-out mice.
  
  
  
  Sciatic nerve-crush injury was induced in wild-type and TLR3 knock-out mice. Histological sections of the sciatic nerve were analyzed for Wallerian degeneration on days 3 and 7 after injury. The level of macrophage infiltration was measured by real-time RT-PCR, flow cytometry and immunohistochemistry. The macrophage-recruiting chemokine gene expressions in the injured nerve were determined by real-time RT-PCR.
  
  
  
  In TLR3 knock-out mice, the nerve injury-induced axonal degeneration and subsequent axonal debris clearance were reduced compared to in wild-type mice. In addition, nerve injury-induced macrophage infiltration into injury sites was attenuated in TLR3 knock-out mice and was accompanied by reduced expression of macrophage-recruiting chemokines such as CC-chemokine ligands (CCL)2/MCP-1, CCL4/MIP-1β and CCL5/RANTES. These macrophage-recruiting chemokines were induced in primary Schwann cells upon TLR3 stimulation. Finally, intraneural injection of polyinosinic-polycytidylic acid, a synthetic TLR3 agonist, induced macrophage infiltration into the sciatic nerve in vivo.
  
  
  
  These data show that TLR3 signaling contributes to Wallerian degeneration after peripheral nerve injury by affecting Schwann cell activation and macrophage recruitment to injured nerves.
authors: Department of Neuroscience and Physiology, and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
authors: Hyunkyoung
authors: H
authors: Lee
authors: Jiyeon
authors: J
authors: Baek
authors: Hyunjung
authors: H
authors: Min
authors: Ik-Hyun
authors: IH
authors: Cho
authors: Seong-Woo
authors: SW
authors: Yu
authors: Sung Joong
authors: SJ
authors: Lee
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D059348:Peripheral Nerve Injuries / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000378:metabolism / Q000473:pathology; D020426:Sciatic Neuropathy / Q000378:metabolism* / Q000473:pathology*; D051196:Toll-Like Receptor 3 / Q000172:deficiency*; D014855:Wallerian Degeneration / Q000378:metabolism* / Q000473:pathology*
chemical_list: C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3