TY - JOUR T1 - <em>S</em>-Adenosyl-<span class="sc">l</span>-homocysteine Hydrolase Inactivation Curtails Ovalbumin-Induced Immune Responses JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1229 LP - 1237 DO - 10.1124/jpet.105.093369 VL - 316 IS - 3 AU - Yun-Feng Fu AU - Jun-Xia Wang AU - Yang Zhao AU - Yang Yang AU - Wei Tang AU - Jia Ni AU - Yi-Na Zhu AU - Ru Zhou AU - Pei-Lan He AU - Chuan Li AU - Xiao-Yu Li AU - Yi-Fu Yang AU - Brian R. Lawson AU - Jian-Ping Zuo Y1 - 2006/03/01 UR - http://jpet.aspetjournals.org/content/316/3/1229.abstract N2 - The reversible S-adenosyl-l-homocysteine (AdoHcy) hydrolase inhibitor methyl 4-(adenin-9-yl)-2-hydroxybutanoate (DZ2002) suppresses macrophage activation and function. The effects of DZ2002 on T cell function, however, are still unclear. Here, we examined whether DZ2002 alters type 1 helper T cell (Th1) and/or type 2 helper T cell (Th2) immune responses, and whether these effects are associated with both the inhibition of AdoHcy hydrolase and intracellular elevation of endogenous AdoHcy. Male C57BL/6 mice immunized with ovalbumin (OVA) were treated with DZ2002 (1, 5, and 25 mg/kg/day) after which lymphocyte proliferation, cytokine production, and IgG responses to OVA were monitored. Administration of DZ2002 dose dependently suppressed OVA-specific lymphocyte proliferation and anti-OVA IgG production compared with controls. Interleukin (IL)-2 and interferon (IFN)-γ as well as anti-OVA IgG2a and IgG3, indicators of Th1 immune responses, were markedly decreased in mice treated with DZ2002, whereas IL-4 and anti-OVA IgG1, indicators of Th2 immune responses, were only mildly suppressed. AdoHcy hydrolase activity in spleens of DZ2002-treated mice was substantially blocked, and not surprisingly, AdoHcy levels were significantly elevated compared with controls. Finally, similar immunosuppressive effects were also observed in mice treated with AdoHcy. These data strongly indicate that DZ2002 suppresses antigen-induced specific immune responses, particularly Th1 responses, through inhibition of AdoHcy hydrolase and elevation of endogenous AdoHcy. ER -