title: Inhibitory effect of IL-17 on neural stem cell proliferation and neural cell differentiation.
abstract: BACKGROUND
  IL-17, a Th17 cell-derived proinflammatory molecule, has been found to play an important role in the pathogenesis of autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). While IL-17 receptor (IL-17R) is expressed in many immune-related cells, microglia, and astrocytes, it is not known whether IL-17 exerts a direct effect on neural stem cells (NSCs) and oligodendrocytes, thus inducing inflammatory demyelination in the central nervous system.
  
  
  METHODS
  We first detected IL-17 receptor expression in NSCs with immunostaining and real time PCR. We then cultured NSCs with IL-17 and determined NSC proliferation by neurosphere formation capability and cell number count, differentiation by immunostaining neural specific markers, and apoptosis of NSCs by flow cytometry.
  
  
  RESULTS
  NSCs constitutively express IL-17R, and when the IL-17R signal pathway was activated by adding IL-17 to NSC culture medium, the number of NSCs was significantly reduced and their ability to form neurospheres was greatly diminished. IL-17 inhibited NSC proliferation, but did not induce cytotoxicity or apoptosis. IL-17 hampered the differentiation of NSCs into astrocytes and oligodendrocyte precursor cells (OPCs). The effects of IL-17 on NSCs can be partially blocked by p38 MAPK inhibitor.
  
  
  CONCLUSIONS
  IL-17 blocks proliferation of NSCs, resulting in significantly reduced numbers of astrocytes and OPCs. Thus, in addition to its proinflammatory role in the immune system, IL-17 may also play a direct role in blocking remyelination and neural repair in the CNS.
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA. zhulin66zhulin@126.com
authors.forename: Zichen
authors.initials: Z
authors.lastname: Li
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.forename: Quancheng
authors.initials: Q
authors.lastname: Kan
authors.forename: Yaping
authors.initials: Y
authors.lastname: Yan
authors.forename: Priyanka
authors.initials: P
authors.lastname: Kumar
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Abdolmohamad
authors.initials: A
authors.lastname: Rostami
authors.forename: Guang-Xian
authors.initials: GX
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D020381:Interleukin-17 / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D011419:Propidium / Q000378:metabolism; D053722:Receptors, Interleukin-17 / Q000378:metabolism; D018874:Spheroids, Cellular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D017304:Annexin A5; D020381:Interleukin-17; D053722:Receptors, Interleukin-17; D011419:Propidium; D048051:p38 Mitogen-Activated Protein Kinases