Colchicine-derived compound CT20126 promotes skin allograft survival by regulating the balance of Th1 and Th2 cytokine production
Experimental & Molecular Medicine
; : 230-238, 2007.
Article
em En
| WPRIM
| ID: wpr-90609
Biblioteca responsável:
WPRO
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-alpha, and IL-1beta, 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-1beta, TNF-alpha, 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.
Palavras-chave
Texto completo:
1
Base de dados:
WPRIM
Assunto principal:
Transplante Homólogo
/
Linhagem Celular
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Colchicina
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Regulação da Expressão Gênica
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Lipopolissacarídeos
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Citocinas
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Terapia de Imunossupressão
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Transplante de Pele
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Fator de Necrose Tumoral alfa
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Teste de Cultura Mista de Linfócitos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Experimental & Molecular Medicine
Ano de publicação:
2007
Tipo de documento:
Article