c-FLIP protects eosinophils from TNF-α-mediated cell death in vivo.

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Gordy, C; Liang, J; Pua, H; He, Y-W

Published Date

  • 2014

Published In

Volume / Issue

  • 9 / 10

Start / End Page

  • e107724 -

PubMed ID

  • 25333625

Pubmed Central ID

  • 25333625

Electronic International Standard Serial Number (EISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0107724

Language

  • eng

Conference Location

  • United States