Anti-inflammatory effect of afatinib (an EGFR-TKI) on OGD-induced neuroinflammation.

Scientific Reports
Yen-Ju ChenA M Y Lin

Abstract

Activated epidermal growth factor receptor (EGFR) has been proposed in the pathophysiology of neurodegenerative diseases. In the present study, the anti-inflammatory effect of afatinib, an EGFR-tyrosine kinase inhibitor (EGFR-TKIs) was investigated using CTX-TNA2 cells and primary cultured astrocytes subjected to oxygen/glucose deprivation (OGD). We found that OGD induced EGFR phosphorylation and activated subsequent signaling pathways, including phosphorylation of AKT and extracellular signal-regulated kinases (ERK). Afatinib blocked OGD-induced phosphorylation of EGFR, AKT and ERK. At the same time, afatinib attenuated OGD-induced elevations in glial fibrillary acidic protein (a biomarker of activated astrocytes) and proliferating cell nuclear antigen expression (a cell proliferating biomarker) as well as hypoxia-induced migratory ability. Furthermore, afatinib decreased OGD-induced increases in cyclooxygenase-II and inducible nitric oxide synthase expression of the treated astrocytes as well as NO content in the culture medium. Moreover, afatinib attenuated OGD-induced caspase 1 activation (a biomarker of inflammasome activation) and interleukin-1β levels (a pro-inflammatory cytokine). Collectively, afatinib could block OGD-...Continue Reading

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Citations

Aug 19, 2020·Cells·Roberta Romano, Cecilia Bucci
Aug 12, 2020·Pharmaceutical Research·Ellen WeisbergJames D Griffin
Jan 9, 2021·Parasitology Research·Anna Zawistowska-DeniziakKatarzyna Basałaj
Dec 29, 2020·Neuropathology and Applied Neurobiology·Conceição BettencourtJanice L Holton
Jun 16, 2021·Scientific Reports·Hui-Ju HuangAnya Maan-Yuh Lin

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
ELISA
confocal microscopy

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