IL-17A Induces MIP-1α Expression in Primary Astrocytes via Src/MAPK/PI3K/NF-kB Pathways: Implications for Multiple Sclerosis

Hongwei Yi, Ying Bai, Xinjian Zhu, Lin lin, Lei Zhao, Xiaodong Wu, Shilpa Buch, Longxin Wang, Jie Chao, Honghong Yao

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Neuroinflammation plays critical roles in multiple sclerosis (MS). In addition to the part played by the lymphocytes, the underlying mechanisms could, in part, be also attributed to activation mediated by astrocytes. Macrophage inflammatory protein-1α (MIP-1α) has been implicated in a number of pathological conditions, specifically attributable to its potent chemottractant effects. Its modulation by IL-17, however, has received very little attention. In the present study, we demonstrated IL-17-mediated induction of MIP-1α in rat primary astroctyes through its binding to the cognate IL-17RA. Furthermore, this effect was mediated via the activation of Src, mitogen-activated protein kinases (MAPKs), PI3K/Akt and NF-kB pathways, culminating ultimately into increased expression of MIP-1α. Exposure of primary mouse astrocytes to IL-17 resulted in increased expression of glial fibrillary acidic protein and, this effect was abrogated in cells cultured in presence of the MIP-1α neutralizing antibody, thus underscoring its role in the activation of astrocytes. In vivo relevance of these findings was further corroborated in experimental autoimmune encephalomyelitis mice that demonstrated significantly increased activation of astrocytes with concomitant increased expression of MIP-1α in the corpus callosum compared with control group. Understanding the regulation of MIP-1α expression may provide insights into the development of potential therapeutic targets for neuroinflammation associated with multiple sclerosis.

Original languageEnglish (US)
Pages (from-to)629-641
Number of pages13
JournalJournal of Neuroimmune Pharmacology
Volume9
Issue number5
DOIs
StatePublished - Oct 24 2014

Keywords

  • Astrocytes
  • IL-17
  • MIP-1α
  • Src

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology

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