Articles

  • the Korean Society for Brain and Neural Sciences

Article

Original Article

Exp Neurobiol 2016; 25(5): 252-261

Published online October 31, 2016

https://doi.org/10.5607/en.2016.25.5.252

© The Korean Society for Brain and Neural Sciences

Comparative Analysis of Protein Tyrosine Phosphatases Regulating Microglial Activation

Gyun Jee Song1, Jaehong Kim1, Jong-Heon Kim1, Seungeun Song1, Hana Park1, Zhong-Yin Zhang2 and Kyoungho Suk1*

1Department of Pharmacology, Brain Science & Engineering Institute, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu 41944, Korea, 2Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, IN 47907, USA

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-53-420-4835, FAX: 82-53-256-1566
e-mail: ksuk@knu.ac.kr

Received: July 27, 2016; Revised: August 21, 2016; Accepted: August 25, 2016

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 RPTPβ) 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 RPTPβ suppressed nitric oxide production in LPS-treated microglial cells in a dose-dependent manner. Furthermore, intracerebroventricular injection of PTP1B, TC-PTP, SHP2, and RPTPβ 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.

Keywords: neuroinflammation, protein tyrosine phosphatase, microglia