TLR3 Agonist Poly-IC Induces IL-33 and Promotes Myelin Repair.

Natarajan C, Yao SY, Sriram S
PLoS One. 2016 11 (3): e0152163

PMID: 27022724 · PMCID: PMC4811556 · DOI:10.1371/journal.pone.0152163

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.

METHODOLOGY AND PRINCIPAL FINDINGS - 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.

CONCLUSION/SIGNIFICANCE - 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.

MeSH Terms (28)

Animals Cell Differentiation Cell Nucleus Cell Polarity Cells, Cultured Corpus Callosum Enzyme Activation Intercellular Signaling Peptides and Proteins Interleukin-33 Lysophosphatidylcholines Macrophages Models, Biological Myelin Basic Protein Myelin Sheath Neuroglia Oligodendroglia p38 Mitogen-Activated Protein Kinases Phenotype Phosphorylation Poly I-C Rats, Sprague-Dawley Real-Time Polymerase Chain Reaction Recombinant Proteins Stem Cells Toll-Like Receptor 3 Transcription, Genetic Up-Regulation Wound Healing

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