Comparative Analysis of Protein Tyrosine Phosphatases Regulating Microglial Activation
Experimental Neurobiology
;
: 252-261, 2016.
Artigo
em Inglês
| WPRIM
| ID: wpr-184904
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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Encéfalo
/
Neuroglia
/
Proteínas Tirosina Fosfatases
/
Microglia
/
Proteína Tirosina Fosfatase não Receptora Tipo 2
/
Óxido Nítrico
Tipo de estudo:
Estudo prognóstico
Idioma:
Inglês
Revista:
Experimental Neurobiology
Ano de publicação:
2016
Tipo de documento:
Artigo
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