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J.-Z. Zhang, K. R. VanDerMeid, M. Salvador-Silva, M. E. Cavet, S. M. Volhejn, K. L. Harrington, Y.-Q. Lin, F. J. López, K. W. Ward; Anti-Inflammatory Effects of BOL-303242-X, a Novel Selective Glucocorticoid Receptor Agonist, in Human Ocular Cells. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5547.
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The aim of this study was to determine the anti-inflammatory effects of BOL-303242-X, a novel selective glucocorticoid receptor agonist under clinical evaluation for the treatment of ophthalmic inflammation, in human ocular cells.
Five primary human ocular cell types, human corneal epithelial cells (HCEpiC), human keratocytes (HK), human conjunctival fibroblasts (HConF), human retinal endothelial cells (HREC), and human optic nerve astrocytes (HONA), were challenged with LPS or IL-1ß and Luminex technology was used to determine the effects of BOL-303242-X on LPS- or IL-1ß-induced multiple cytokine release into the medium. Dexamethasone (DEX) or triamcinolone acetonide (TA) was used as the control.
LPS or IL-1ß induced measurable cytokine release in all cell types studied, 8 out of 12 in HCEpiC, 6 out of 18 in HK, 10 out of 18 in HConF, 8 out of 12 in HREC, and 5 out of 6 in HONA. BOL-303242-X significantly reduced LPS- or IL-1ß-induced cytokine release in a dose-dependent manner for IL-6, IL-8, and MCP-1, having comparable efficacy to that of DEX or TA. The different cell types had different sensitivities to the inhibitory effects of BOL-303242-X. To help place these data into context with systemic inflammatory responses, THP-1, a human monocytic cell line, was also employed for comparison purposes. The range of sensitivity for the different cell types for IL-6 levels was THP-1 = HConF/HK > HCEpiC > HONA > HREC.
BOL-303242-X acts as an anti-inflammatory agent in various human ocular cells. BOL-303242-X may be used in the treatment of ocular inflammation with reduced side effects as compared to glucocorticoids such as the induction of intraocular pressure (IOP) and cataract.
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