2014 journal article

c-FLIP Protects Eosinophils from TNF-α-Mediated Cell Death In Vivo

PLoS ONE, 9(10), e107724.

By: C. Gordy* , J. Liang *, H. Pua * & Y. He *

Ed(s): H. Nakano

MeSH headings : Animals; Apoptosis / drug effects; Bone Marrow Cells / cytology; Bone Marrow Transplantation; CASP8 and FADD-Like Apoptosis Regulating Protein / genetics; CASP8 and FADD-Like Apoptosis Regulating Protein / metabolism; Cells, Cultured; Chromosomes, Artificial, Bacterial / genetics; Eosinophils / cytology; Eosinophils / drug effects; Eosinophils / metabolism; Genotype; Mice; Mice, Transgenic; NF-kappa B / metabolism; Tumor Necrosis Factor-alpha / pharmacology; Up-Regulation / drug effects
TL;DR: It is shown for the first time that eosinophils express the caspase 8-inhibitory protein c- FLIP, and c-FLIP expression is upregulated upon TNF-α stimulation, and this suggests c-FlIP as a potential therapeutic target for the treatment of eOSinophil-mediated disease. (via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being (OpenAlex)
Source: ORCID
Added: August 24, 2021

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.