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C. Bucolo, A.R. Qasem, A. Maltese, M. Cro, S. Spampinato; Potential Anti-Inflammatory Action of Cloricromene at Ocular Level: Blockade of Integrin-Mediated Cell Adhesion . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2239.
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Purpose: Cloricromene has antiplatelet and anti-leukocyte properties; it decreases superoxide anion production and inhibits chemotaxis as well as adhesion of monocytes/macrophages to endothelial cells. It has been previously reported that cloricromene protects against endotoxin-induced uveitis in rats (C. Bucolo et al., Invest. Ophthalmol. Vis. Sci. 44, 2003, in press). Despite extensive research efforts, molecular mechanisms of cloricromene’s action are still poor understood. The aim of this study was to evaluate any activity of cloricromene as inhibitor of α4ß1 and αLß2 integrins since they play a relevant role in several ocular inflammatory diseases. Methods: Cloricromene was assayed for α4ß1 and αLß2 integrin activity in a cell-based assay. 5-Chloromethylfluorescein diacetate-labeled Jurkat cells (clone E6.1) were allowed to bind, in 96-well plates, to soluble human vascular cell adhesion molecule-1 (VCAM-1) and soluble intracellular adhesion molecule-1 (ICAM-1), respectively, in the presence of several concentrations of cloricromene. Adherent cells were quantified by fluorometry. Results: Cloricromene was found to inhibit, in a concentration-related manner, Jurkat cell adhesion to VCAM-1 coated plates (IC50= 405.8 µM; 95% confidence limits: 274.5-599.9; n=4); similarly, it blocked cell adhesion to ICAM-1 coated plates. Specificity of Jurkat cell adhesion, mediated by VCAM-1 or ICAM-1, was confirmed by confocal microscopy and suitable antibodies. Conclusions: This study reports, for the first time, that cloricromene acts as an inhibitor of cell adhesion mediated by α4ß1 and αLß2 integrins. This action may contribute to the anti-inflammatory effect elicited by this compound at ocular level. Moreover, this assay could be employed to evaluate novel, potential drugs useful to treat inflammatory and allergic eye diseases.
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