TY - JOUR T1 - Oral Administration of 1,4-Aryl-2-mercaptoimidazole Inhibits T-Cell Proliferation and Reduces Clinical Severity in the Murine Experimental Autoimmune Encephalomyelitis Model JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1005 LP - 1013 DO - 10.1124/jpet.109.154948 VL - 331 IS - 3 AU - Eun Joo Jung AU - Minkyu Hur AU - Young Lim Kim AU - Ge Hyeong Lee AU - Jeongmin Kim AU - Ikyon Kim AU - MinWoo Lee AU - Ho-Kyun Han AU - Mi-Soon Kim AU - Sejin Hwang AU - Sungjoo Kim AU - A. Mi Woo AU - Yeup Yoon AU - Heon Jin Park AU - Jonghwa Won Y1 - 2009/12/01 UR - http://jpet.aspetjournals.org/content/331/3/1005.abstract N2 - T cells play a pivotal role in the initiation and progression of multiple sclerosis. We have found that 1,4-aryl-2-mercaptoimidazole (KRM-III) inhibited T-cell antigen receptor- and phorbol myristate acetate/ionomycin-induced activation of nuclear factor of activated T cells (NFAT) and T-cell proliferation with an IC50 of 5 μM. The KRM-III-mediated inhibitory effect was specific for NFAT activation but not for nuclear factor κB. Oral administration of 90 mg/kg KRM-III resulted in complete abrogation of anti-CD3 antibody-induced T-cell activation and a 45.8% reduction in footpad swelling in bovine serum albumin-induced delayed-type hypersensitivity. In the murine experimental autoimmune encephalomyelitis (EAE) model, oral administration of KRM-III significantly attenuated the severity of disease when given before or after disease onset. Draining lymph node cells from KRM-III-treated mice showed markedly reduced proliferation in response to myelin oligodendrocyte glycoprotein peptide. Histological analysis indicated that KRM-III reduced the infiltration of inflammatory cells to the white matter of spinal lumbar cords. These results demonstrate that KRM-III efficiently inhibits T-cell activation and inflammatory responses and lessens EAE clinical signs, which suggest KRM-III as a potential lead compound for the treatment of T-cell-driven autoimmune diseases.© 2009 by The American Society for Pharmacology and Experimental Therapeutics ER -