Comparison of effects of Y-27632 and Isoproterenol on release of cytokines from human peripheral T cells

Y-27632 selectively inhibits Rho-associated protein kinases (ROCKs), an effector for RhoA. The RhoA system is involved in T cell activation. Y-27632 mimicked effects of beta agonists on human cells. We examined the effects of both Y-27632 and Isoproterenol (Iso) on the release of T helper type I (Th-1) cytokines (interleukin (IL)-2 and interferon (IFN)-gamma) and Th-2 cytokines (IL-4 and IL-5) from activated human T cells. Peripheral T cells obtained from seven healthy volunteers were incubated in the presence of Y-27632 (0.1-10 muM) for 30 min, and stimulated with 50 mug/ml of Concanavalin A (Con A) for 24 h. Concomitantly, after an incubation with medium alone, cells were stimulated with Con A in the presence of Iso (0.1-10 muM). The concentration of these cytokines in supernatants was measured by ELISA. Both Y-27632 and Iso suppressed release of Th-1 cytokines, decreased release of Th-2 cytokines weakly, and reduced ratio of Th-1/Th-2 cytokine release from Con A-activated T cells. These inhibitory effects of Y-27632 closely resembled those of Iso at each concentration tested. Y-27632 mimicked effects of Iso on secretion of Th-1 and Th-2 cytokines from human peripheral T cells activated with Con A. It is suggested that the RhoA/ROCK system plays an important role in the release of Th-1 cytokines and is partially involved in the release of Th-2 cytokines from human T cells activated through T cell receptor (TCR). (C) 2003 Elsevier B.V. All fights reserved.