Exp Neurobiol.  2013 Dec;22(4):268-276. 10.5607/en.2013.22.4.268.

The Effect of Agmatine on Expression of IL-1beta and TLX Which Promotes Neuronal Differentiation in Lipopolysaccharide-Treated Neural Progenitors

Affiliations
  • 1Department of Anatomy, Yonsei University College of Medicine, Seoul 120-752, Korea. jelee@yuhs.ac
  • 2BK21 Plus Project for Medical Sciences, Yonsei University College of Medicine, Seoul 120-752, Korea.

Abstract

Differentiation of neural progenitor cells (NPCs) is important for protecting neural cells and brain tissue during inflammation. Interleukin-1 beta (IL-1beta) is the most common pro- inflammatory cytokine in brain inflammation, and increased IL-1beta levels can decrease the proliferation of NPCs. We aimed to investigate whether agmatine (Agm), a primary polyamine that protects neural cells, could trigger differentiation of NPCs by activating IL-1beta in vitro. The cortex of ICR mouse embryos (E14) was dissociated to culture NPCs. NPCs were stimulated by lipopolysaccharide (LPS). After 6 days, protein expression of stem cell markers and differentiation signal factors was confirmed by using western blot analysis. Also, immunocytochemistry was used to confirm the cell fate. Agm treatment activated NPC differentiation significantly more than in the control group, which was evident by the increased expression of a neuronal marker, MAP2, in the LPS-induced, Agm-treated group. Differentiation of LPS-induced, Agm-treated NPCs was regulated by the MAPK pathway and is thought to be related to IL-1beta activation and decreased expression of TLX, a transcription factor that regulates NPC differentiation. Our results reveal that Agm can promote NPC differentiation to neural stem cells by modulating IL-1beta expression under inflammatory condition, and they suggest that Agm may be a novel therapeutic strategy for neuroinflammatory diseases.

Keyword

agmatine; neural progenitor cell (NPC); differentiation; lipopolysaccharide; IL-1beta; TLX

MeSH Terms

Agmatine*
Animals
Blotting, Western
Brain
Embryonic Structures
Encephalitis
Immunohistochemistry
Inflammation
Interleukin-1beta
Mice
Mice, Inbred ICR
Neural Stem Cells
Neurons*
Stem Cells
Transcription Factors
Agmatine
Interleukin-1beta
Transcription Factors
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