Colchicine-derived compound CT20126 promotes skin allograft survival by regulating the balance of Th1 and Th2 cytokine production

Seon Jin Lee, Seung Namkoong, Kwon Soo Ha, Woo Dong Nam, Young Guen Kwon, Hansoo Lee, Eun Young Yoon, Dong Jo Chang, Soon Ok Kim, Young Myeong Kim

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Colchicine has been shown to regulate the expression of inflammatory gene, but this compound possesses much weaker anti-inflammatory activity. In this study, we synthesized a new colchicine derivative CT20126 and examined its immunomodulatory property. CT20126 was found to have immunosuppressive effects by inhibiting lymphocyte proliferation without cytotoxicity and effectively inhibit the transcriptional expression of the inflammatory genes, iNOS, TNF-α, and IL-1β, in macrophages stimulated by LPS. This effect was nearly comparable to that of cyclosporine A. This compound also significantly suppressed the production of nitric oxide and Th1-related pro-inflammatory cytokines, IL-1β, TNF-α, and IL-2, with minimal suppression of Th2-related anti-inflammatory cytokines IL-4 and IL-10 in the sponge matrix allograft model. Moreover, administration of CT20126 prolonged the survival of allograft skins from BALB/c mice (H-2d) to the dorsum of C57BL/6 (H-2b) mice. The in vivo immune suppressive effects of CT20126 were similar to that of cyclosporine A. These results indicate that this compound may have potential therapeutic value for transplantation rejection and other inflammatory diseases.

Original languageEnglish
Pages (from-to)230-238
Number of pages9
JournalExperimental and Molecular Medicine
Volume39
Issue number2
DOIs
Publication statusPublished - 2007 Apr 30

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

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