http://scholars.nricm.edu.tw/handle/123456789/47
Title: | Anti-inflammatory effect of afatinib (an EGFR-TKI) on OGD-induced neuroinflammation | Authors: | Chen, Yen-Ju Hsu, Chia-Chi Shiao, Young-Ji Wang, Hsiang-Tsui Lo, Yu-Li Lin, Anya Maan-Yuh |
Issue Date: | 2019 | Journal: | Scientific Reports | 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-1�] levels (a pro-inflammatory cytokine). Collectively, afatinib could block OGD-induced EGFR activation and its downstream signaling pathways in astrocytes. Moreover, afatinib attenuated OGD-induced astrocyte activation, proliferation and inflammasome activation. These data support the involvement of EGFR activation in neuroinflammation. Furthermore, EGFR-TKIs may be promising in inhibiting neuroinflammation in the CNS neurodegenerative diseases. | Description: | Scientific Reports 9(1): 2516 | URI: | http://localhost/handle/123456789/47 | DOI: | 10.1038/s41598-019-38676-7 |
Appears in Collections: | 張芳榮 |
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