1. c-FLIP Protects Eosinophils from TNF-α-Mediated Cell Death In Vivo.
- Author
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Gordy, Claire, Liang, Jie, Pua, Heather, and He, You-Wen
- Subjects
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CELL death , *EOSINOPHILS , *TUMOR necrosis factors , *APOPTOSIS , *PROTEIN expression - Abstract
Understanding the signals that regulate eosinophil survival and death is critical to developing new treatments for asthma, atopy, and gastrointestinal disease. Previous studies suggest that TNF-α stimulation protects eosinophils from apoptosis, and this TNF-α-mediated protection is mediated by the upregulation of an unknown protein by NF-κB. Here, we show for the first time that eosinophils express the caspase 8-inhibitory protein c-FLIP, and c-FLIP expression is upregulated upon TNF-α stimulation. Considering that c-FLIP expression is regulated by NF-κB, we hypothesized that c-FLIP might serve as the “molecular switch” that converts TNFRI activation to a pro-survival signal in eosinophils. Indeed, we found that one c-FLIP isoform, c-FLIPL, is required for mouse eosinophil survival in the presence of TNF-α both in vitro and in vivo. Importantly, our results suggest c-FLIP as a potential therapeutic target for the treatment of eosinophil-mediated disease. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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