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Oral Administration of 1,4-aryl-2-mercaptoimidazole Inhibits T-cell Proliferation and Reduces Clinical Severity in the Murine Experimental Autoimmune Encephalomyelitis Model

Oral Administration of 1,4-aryl-2-mercaptoimidazole Inhibits T-cell Proliferation and Reduces Clinical Severity in the Murine Experimental Autoimmune Encephalomyelitis Model

Eun Joo Jung, Minkyu Hur, Young Lim Kim, Ge Hyeong Lee, Jeongmin Kim, Ikyon Kim, Minwoo Lee, Ho-Kyun Han, Mi-Soon Kim, Sejin Hwang, Sungjoo Kim, A Mi Woo, Yeup Yoon, Heon Jin Park, Jonghwa Won

J Pharmacol Exp Ther. 2009 Dec;331(3):1005-13.

PMID: 19741152

Abstract:

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 IC(50) of 5 microM. The KRM-III-mediated inhibitory effect was specific for NFAT activation but not for nuclear factor kappaB. 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP79220943	KRM-III		79220-94-3	Price

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