Cytokine-dependent ELAM-1 induction and concomitant intraocular pressure regulation in porcine anterior eye perfusion culture.

ABSTRACT

PURPOSE: To demonstrate the capacity of interleukin (IL)-1 to simultaneously lower intraocular pressure (IOP) and induce trabecular ELAM-1 expression in one experiment and to test for IL-6 accordingly and evaluate the role of transforming growth factor (TGF)-ß2 as an IL-1 antagonist. METHODS: Forty-two porcine eyes were subjected to trabecular meshwork (TM) perfusion with IL-1α, -1ß, or -6 for 48 hours. Twelve of the IL-1α-treated eyes also received TGF-ß2 for the final 24-hour period. Polymerase chain reaction and Western blot analyses of ELAM-1 expression were then performed on harvested TM samples. mRNA regulation of IL-1α, IL-1ß, IL-6, TGF-ß2, and P-selectin (SELP) was determined. RESULTS: IL-1α and -1ß treatment augmented outflow facility approximately threefold while inducing ELAM-1. IL-6 perfusion neither changed IOP nor induced ELAM-1. IL-1α/TGF-ß2 double treatment significantly counteracted the IL-1-induced IOP decrease and markedly reduced the degree of ELAM-1 mRNA upregulation from 22.3- to 3.1-fold, and ELAM-1 protein from 1.9- to 1.2-fold. IL-1α mRNA was upregulated 5.3-, 3.3-, and 5.5-fold after perfusion with IL-1α, -1ß, and -1α/TGF-ß2, respectively. The respective values for IL-6 mRNA were 2.0-, 2.1- and 2.4-fold. Expression of IL-1ß and TGF-ß2 mRNA remained unchanged. IL-6 perfusion had no discernible regulatory effect. CONCLUSIONS: Simultaneous demonstration of IL-1's lowering of IOP and inducing trabecular ELAM-1 was achieved for the first time in one experiment, and its possible implications in the pathogenesis of glaucoma was further emphasized. The involvement of an autocrine feedback loop was confirmed in the porcine system. TGF-ß2 constitutes a potent IL-1 antagonist for IOP and ELAM-1 regulation.