Comparative analysis of protein tyrosine phosphatases regulating microglial activation

Gyun Jee Song, Jaehong Kim, Jong Heon Kim, Seungeun Song, Hana Park, Zhong Yin Zhang, Kyoungho Suk

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Protein tyrosine phosphatases (PTPs) are key regulatory factors in inflammatory signaling pathways. Although PTPs have been extensively studied, little is known about their role in neuroinflammation. In the present study, we examined the expression of 6 different PTPs (PTP1B, TC-PTP, SHP2, MEG2, LYP, and RPTPß) and their role in glial activation and neuroinflammation. All PTPs were expressed in brain and glia. The expression of PTP1B, SHP2, and LYP was enhanced in the inflamed brain. The expression of PTP1B, TC-PTP, and LYP was increased after treating microglia cells with lipopolysaccharide (LPS). To examine the role of PTPs in microglial activation and neuroinflammation, we used specific pharmacological inhibitors of PTPs. Inhibition of PTP1B, TC-PTP, SHP2, LYP, and RPTPß suppressed nitric oxide production in LPS-treated microglial cells in a dose-dependent manner. Furthermore, intracerebroventricular injection of PTP1B, TC-PTP, SHP2, and RPTPß inhibitors downregulated microglial activation in an LPS-induced neuroinflammation model. Our results indicate that multiple PTPs are involved in regulating microglial activation and neuroinflammation, with different expression patterns and specific functions. Thus, PTP inhibitors can be exploited for therapeutic modulation of microglial activation in neuroinflammatory diseases.

Original languageEnglish (US)
Pages (from-to)252-261
Number of pages10
JournalExperimental Neurobiology
Volume25
Issue number5
DOIs
StatePublished - Oct 1 2016

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Keywords

  • Microglia
  • Neuroinflammation
  • Protein tyrosine phosphatase

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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