The Anti-Inflammatory Effects of the Small Molecule Pifithrin-micro on BV2 Microglia

Fleiss, B, Chhor, V, Rajudin, N, Lebon, S, Hagberg, H, Gressens, P and Thornton, C 2015, 'The Anti-Inflammatory Effects of the Small Molecule Pifithrin-micro on BV2 Microglia', Developmental Neuroscience, vol. 37, no. 45, pp. 363-375.


Document type: Journal Article
Collection: Journal Articles

Title The Anti-Inflammatory Effects of the Small Molecule Pifithrin-micro on BV2 Microglia
Author(s) Fleiss, B
Chhor, V
Rajudin, N
Lebon, S
Hagberg, H
Gressens, P
Thornton, C
Year 2015
Journal name Developmental Neuroscience
Volume number 37
Issue number 45
Start page 363
End page 375
Total pages 13
Publisher S. Karger AG
Abstract Neonatal encephalopathy (NE) is a leading cause of childhood death and disability in term infants. Treatment options for perinatal brain injury are limited and developing therapies that target multiple pathways within the pathophysiology of NE are of great interest. Pifithrin-µ (PFT-µ) is a drug with striking neuroprotective abilities in a preclinical model of hypoxia-ischemia (HI)-induced NE wherein cell death is a substantial cause of injury. Work from neurons and tumor cells reports that PFT-µ is able to inhibit p53 binding to the mitochondria, heat shock protein (HSP)-70 substrate binding and activation of the NF-kB pathway. The purpose of this study is to understand whether the neuroprotective effects of PFT-µ also include direct effects on microglia. We utilized the microglial cell line, BV2, and we studied the dose-dependent effect of PFT-µ on M1-like and M2-like phenotype using qRT-PCR and Western blotting, including the requirement for the presence of p53 or HSP-70 in these effects. We also assessed phagocytosis and the effects of PFT-µ on genes within metabolic pathways related to phenotype. We noted that PFT-µ robustly reduced the M1-like (lipopolysaccharide, LPS-induced) BV2 response, spared the LPS-induced phagocytic ability of BV2 and had no effect on the genes related to metabolism and that effects on phenotype were partially dependent on the presence of HSP-70 but not p53. This study demonstrates that the neuroprotective effects of PFT-µ in HI-induced NE may include an anti-inflammatory effect on microglia and adds to the evidence that this drug might be of clinical interest for the treatment of NE.
Subject Innate Immunity
Neurology and Neuromuscular Diseases
Paediatrics
Keyword(s) Neuroinflammation
Phenotype
Neuroprotective
2-phenylethynesulfonamide
Pifithrin-µ
DOI - identifier 10.1159/000370031
Copyright notice © 2015 S. Karger AG, Basel
ISSN 1421-9859
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