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 1 (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 micro M) for 30 min, and stimulated with 50 micro g/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 micro M). 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).
Aihara
Masayuki
M
First Department of Internal Medicine, Gunma University Faculty of Medicine, School of Medicine, 3-39-15, Showa-machi, Maebashi, Gunma 371-8511, Japan. aiharam@showa.gunma-u.ac.jp
Dobashi
Kunio
K
Iizuka
Kunihiko
K
Nakazawa
Tsugio
T
Mori
Masatomo
M
D000577:Amides / Q000494:pharmacology*; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
D000577:Amides; D016207:Cytokines; D007376:Interleukin-2; D015848:Interleukin-5; D011725:Pyridines; D003208:Concanavalin A; C108830:Y 27632; D015847:Interleukin-4; D007371:Interferon-gamma; D007545:Isoproterenol