Abstract

BackgroundImpaired 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 FindingsWe 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/SignificanceOur 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.

Highlights

  • Recognition of invading pathogens is mediated by the activation of innate and adaptive arms of the immune response.[1]

  • We quantitated mRNA of Mbp, myelin oligodendrocyte protein (Mog) and proteolipoprotein (Plp) along with mRNAs of Purα, Sox10 and Sp1 in oligodendrocyte precursor cells (OPC) cultured with poly-IC

  • To test whether IL-33 mediated increase of MBP in OPC is regulated by p38MAPK, we examined the expression of MBP in the presence of p38MAPK inhibitor SB 203580

Read more

Summary

Introduction

Recognition of invading pathogens is mediated by the activation of innate and adaptive arms of the immune response.[1]. Poly-IC and IL-33 Activate Myelin Genes pathogen associated molecular pattern (PAMP) receptors which recognize common structures present in bacteria and viruses. The receptors which mediate innate immune response are expressed either on the cell surface or present in the cytosol of many cell types, including the cells of the CNS [1]. In inflammatory demyelinating disease of the central nervous system (CNS), 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.

Methods
Results
Discussion
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call