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Journal article
Effect of IL-5, glucocorticoid, and Fas ligation on Bcl-2 homologue expression and caspase activation in circulating human eosinophils
Clinical and experimental immunology, v 120(1), 12
Apr 2000
PMID: 10759758
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
SUMMARY IL-5 is a potent eosinophil viability-enhancing factor that has been strongly implicated in the pathogenesis of IgE-mediated inflammation in vivo. Recently published data have suggested that IL-5 (and related cytokines) may act by altering the expression of the anti-apoptotic regulator Bcl-2 or its homologues, but this is controversial. The behaviour of the recently described pro-apoptotic cysteine proteases (caspases) in eosinophils after IL-5 treatment has not been explored. We examined the effect of IL-5 on the expression of four major Bcl-2 homologues, as well as on the expression/activation of key members of the caspase cell death cascade in cultured circulating human eosinophils. The effect of relevant inducers of eosinophil apoptosis (glucocorticoid and Fas ligation) on these regulatory proteins was also examined. We observed baseline expression of the anti-apoptotic Mcl-1 and pro-apoptotic Bax proteins in immunoblots of eosinophil lysates, but not Bcl-x, Bcl-2. IL-5 treatment had the effect of maintaining this basal level of expression over time without altering the balance of Bcl-2 homologues. The (upstream) caspase 8 and (downstream) caspase 3 proenzymes were detected in eosinophils at baseline, and were processed during spontaneous and stimulated eosinophil death. IL-5 completely blocked caspase processing in spontaneous and dexamethasone-induced cell death, and significantly slowed processing during Fas ligation. Our data do not support the theory that IL-5 acts by altering the balance of anti-apoptotic and pro-apoptotic Bcl-2 homologues, but suggest that it may act by regulating activation of the caspase cell death cascade.
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Details
- Title
- Effect of IL-5, glucocorticoid, and Fas ligation on Bcl-2 homologue expression and caspase activation in circulating human eosinophils
- Creators
- J Zangrilli - Department of Medicine, Division of Critical Care, Pulmonary, Allergic and Immunologic DiseasesN Robertson - Thomas Jefferson UniversityA Shetty - Department of Medicine, Division of Critical Care, Pulmonary, Allergic and Immunologic DiseasesJ Wu - Department of Medicine, Division of Critical Care, Pulmonary, Allergic and Immunologic DiseasesA Hastie - Department of Medicine, Division of Critical Care, Pulmonary, Allergic and Immunologic DiseasesJ E Fish - Department of Medicine, Division of Critical Care, Pulmonary, Allergic and Immunologic DiseasesG Litwack - Thomas Jefferson UniversityS P Peters - Department of Medicine, Division of Critical Care, Pulmonary, Allergic and Immunologic Diseases
- Publication Details
- Clinical and experimental immunology, v 120(1), 12
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- SOM Dean - Research Administration
- Web of Science ID
- WOS:000086163800004
- Scopus ID
- 2-s2.0-0034107113
- Other Identifier
- 991021463427604721
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- Web of Science research areas
- Immunology