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C. Bucolo, J. Z. Zhang, K. W. Ward, A. Spartà, M. Baiula, S. Spampinato; Effects of BOL-303242-X, a Selective Glucocorticoid Receptor Agonist (SEGRA), on Human Eosinophils and an Ocular Allergy Model. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6323.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the effects of BOL-303242-X, a selective glucocorticoid receptor agonist (SEGRA), in human eosinophils and in a model of ocular allergy.
To assess glucocorticoid-induced apoptosis and cytokine-induced eosinophil survival, EoL-1 cells were double-stained with annexin V-Fluos and propidium iodide, and analyzed in a flow cytometry system. FACS analysis were performed to assess the induction of surface expression of annexin-I and CXCR4. EoL-1 and HMC-1 were incubated with BOL-303242-X or dexamethasone (DEX), and cytokine levels measured using Luminex 200TM (Luminex, Austin, TX). The guinea pig model of allergic conjunctivitis was used to investigate the effects of BOL-303242-X in comparison with DEX. Statistical analysis was performed by ANOVA and Newman-Keuls post-hoc test using GraphPad (San Diego, CA).
BOL-303242-X induced EoL-1 apoptosis in a concentration- and time-dependent manner. BOL-303242-X reversed GM-CSF- or IL-5-induced eosinophil survival and showed higher anti-inflammatory activity than that of DEX. Flow cytometry assays demonstrated that BOL-303242-X up to 1 µM did not significantly increase CXCR4 or annexin-1 expression in EoL-1 cells, while the same concentration of DEX did. BOL-303242-X was able to significantly reduce the release of IL-8, whereas the same concentration (1 µM) of DEX did not produce the same effect. BOL-303242-X blocked the release of the majority of pro-inflammatory cytokines in HMC-1 cells. BOL-303242-X significantly reduced (p<0.001) the clinical symptoms of allergic conjunctivitis as well as eosinophil infiltration showing higher potency than DEX.
These results suggest that in eosinophils BOL-303242-X acts as a more potent anti-inflammatory than DEX and unlike DEX, BOL-303242-X does not increase CXCR4 and annexin-I expression. BOL-303242-X was a potent repressor of cytokine expression in eosinophils and mast cells. Finally, in guinea pigs, BOL-303242-X more potent than DEX at reducing clinical symptoms of allergic conjunctivitis. These findings indicate that BOL-303242-X is an effective agent in the treatment of ocular inflammation conditions like allergic diseases.
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