title: TLR3 Agonist Poly-IC Induces IL-33 and Promotes Myelin Repair.
abstract: BACKGROUND
  Impaired remyelination of demyelinated axons is a major cause of neurological disability. In inflammatory demyelinating disease of the central nervous system (CNS), although remyelination does happen, it is often incomplete, resulting in poor clinical recovery. Poly-IC a known TLR3 agonist and IL-33, a cytokine which is induced by poly-IC are known to influence recovery and promote repair in experimental models of CNS demyelination.
  
  
  RESULTS
  We examined the effect of addition of poly-IC and IL-33 on the differentiation and maturation of oligodendrocyte precursor cells (OPC) cultured in vitro. Both Poly-IC and IL-33 induced transcription of myelin genes and the differentiation of OPC to mature myelin forming cells. Poly-IC induced IL-33 in OPC and addition of IL-33 to in vitro cultures, amplified further, IL-33 expression suggesting an autocrine regulation of IL-33. Poly-IC and IL-33 also induced phosphorylation of p38MAPK, a signaling molecule involved in myelination. Following the induction of gliotoxic injury with lysolecithin to the corpus callosum (CC), treatment of animals with poly-IC resulted in greater recruitment of OPC and increased staining for myelin in areas of demyelination. Also, poly-IC treated animals showed greater expression of IL-33 and higher expression of M2 phenotype macrophages in the CC.
  
  
  CONCLUSIONS
  Our studies suggest that poly-IC and IL-33 play a role in myelin repair by enhancing expression of myelin genes and are therefore attractive therapeutic agents for use as remyelinating agents in human demyelinating disease.
authors.affiliation: Department of Neurology, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Chandramohan
authors.initials: C
authors.lastname: Natarajan
authors.affiliation: Department of Neurology, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Song-Yi
authors.initials: SY
authors.lastname: Yao
authors.affiliation: Department of Neurology, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Sriram
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D016764:Cell Polarity / Q000187:drug effects; D002478:Cells, Cultured; D003337:Corpus Callosum / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D000067596:Interleukin-33 / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D010766:Phosphorylation / Q000187:drug effects; D011070:Poly I-C / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000494:pharmacology; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000819:agonists* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D000067596:Interleukin-33; D008244:Lysophosphatidylcholines; D004676:Myelin Basic Protein; D011994:Recombinant Proteins; D051196:Toll-Like Receptor 3; D048051:p38 Mitogen-Activated Protein Kinases; D011070:Poly I-C