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, Min Woo Lee, Ho Kyun Han, Mi Soon Kim, Sejin Hwang, Sungjoo Kim, A. Mi Woo, Yeup Yoon, Heon Jin Park, Jonghwa Won

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

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 μM. The KRM-III-mediated inhibitory effect was specific for NFAT activation but not for nuclear factor kB. 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 KRMIII 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 KRMIII as a potential lead compound for the treatment of T-celldriven autoimmune diseases.

Original languageEnglish
Pages (from-to)1005-1013
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume331
Issue number3
DOIs
Publication statusPublished - 2009 Dec

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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