Oral Administration of 1,4-Aryl-2-mercaptoimidazole Inhibits T-Cell Proliferation and Reduces Clinical Severity in the Murine Experimental Autoimmune Encephalomyelitis Model
- Authors
- Jung, Eun Joo; Hur, Minkyu; Kim, Young Lim; Lee, Ge Hyeong; Kim, Jeongmin; Kim, Ikyon; Lee, MinWoo; Han, Ho-Kyun; Kim, Mi-Soon; Hwang, Sejin; Kim, Sungjoo; Woo, A. Mi; Yoon, Yeup; Park, Heon Jin; Won, Jonghwa
- Issue Date
- Dec-2009
- Publisher
- AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
- Citation
- JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, v.331, no.3, pp.1005 - 1013
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
- Volume
- 331
- Number
- 3
- Start Page
- 1005
- End Page
- 1013
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/175750
- DOI
- 10.1124/jpet.109.154948
- ISSN
- 0022-3565
- 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 IC50 of 5 mu M. The KRM-III-mediated inhibitory effect was specific for NFAT activation but not for nuclear factor kappa B. 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.
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