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K.K. Sra, S.D. Trocme; Effect of Nedocromil Sodium on Induced Expression of ICAM-1 and RANTES from Cultured Conjunctival Cells . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3741.
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Purpose: Intercellular adhesion molecule-1 (ICAM-1) and the chemokine RANTES are expressed by conjunctival epithelial cells (CECs) during allergic disease. They help recruit and retain leucocytes, inflammatory cells characteristic of the late phase allergic response and of chronic allergic disease. These experiments investigated whether nedocromil sodium, which acts by mast cell stabilization and inhibition of inflammatory cell recruitment, could inhibit expression of ICAM-1 or RANTES by human CECs. Methods: A CEC cell-line transfected with plasmid RSV-T to improve stability was passed (at 90% confluency) 18-22 times. Confluent cells were preincubated with 10-7 or 10-5 M nedocromil sodium before induction. ICAM-1 expression was induced by 100U/mL interferon γ (IFN-γ) and assayed later by cell-based ELISA. RANTES was induced by 50 µg/mL major basic protein (MBP) and then assayed in the cell supernatant by ELISA. Results: IFN-γ induced ICAM-1 by 2.8-fold at 6 hours and 7.7-fold at 24 hours. For both assay time points, 10-7 M nedocromil (41 ng/mL) preincubation for 1 hour decreased ICAM-1 induction by >50%. Preincubation up to 4 hours and/or with a 100-fold greater concentration of nedocromil afforded similar decreases, all statistically significant (P<.05). MBP induced RANTES release by 23-, 4.2-, and 2.3-fold, after 1, 3, and 6 hours respectively. Preincubation with 10-7 or 10-5 M nedocromil decreased the amount of RANTES released to 53-93% of full induction. Preincubation for 4 hours with 10-5 M nedocromil afforded a statistically significant reduction (P<.05). Conclusions: Inhibition of ICAM-1 and RANTES induction in cultured human conjunctival epithelial cells is consistent with the ability of nedocromil sodium to inhibit recruitment of inflammatory cells and reinforces the model of its anti-allergic activity by multiple mechanisms.
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