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Megan E. Cavet, Stepan M. Volhejn, Karen L. Harrington, Thomas Vollmer, Keith W. Ward, Jin-Zhong Zhang; Anti-Allergic Effects of Mapracorat, a Novel Selective Glucocorticoid Receptor Agonist, in Human Conjunctival Fibroblasts and Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6422.
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The aim of this study was to determine the ocular anti-allergic effects of mapracorat, a novel selective glucocorticoid receptor agonist (SEGRA) with corticosteroid-like anti-inflammatory activities and reduced transactivation-mediated side effects such as elevation of intraocular pressure, in human ocular cells.
Two primary human conjunctival cell types, human conjunctival fibroblasts (HConF) and human conjunctival epithelial cells (HConEpiC), were challenged with IL-4 or IL-13 plus TNF-α and Luminex technology was used to determine the effects of mapracorat on the release of eotaxin and RANTES, two allergy-related chemokines, as well as proinflammatory cytokines. Dexamethasone (DEX) was used as the control.
IL-13 plus TNF-α in HConF significantly increased eotaxin-1, RANTES and numerous pro-inflammatory cytokines. Mapracorat significantly reduced IL-13 plus TNF-α-induced eotaxin-1, IL-6, IL-8, MCP-1 and RANTES release in a dose-dependent manner, having comparable efficacy to that of DEX. Significant inhibition was observed at 10 nM mapracorat. In HConEpiC, IL-4 plus TNF-α increased RANTES and multiple pro-inflammatory cytokines. Both mapracorat and DEX significantly reduced IL-4 plus TNF-α-induced RANTES, CTACK, GM-CSF, IL-6, IP-10 and MCP-1 release in a dose-dependent manner in this cell type. Inhibition was observed at a dose of 10 nM mapracorat for the majority of the induced chemokines/cytokines.
Data from these in vitro models indicate that mapracorat is efficacious and potent in reducing IL-4 or IL-13 plus TNF-α-induced the release of allergy-related chemokines and proinflammatory cytokines from HConF and HConEpiC, supporting clinical evaluation of the compound in reducing allergic and inflammatory reactions in allergic conjunctivitis.
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