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Colchicine-derived compound CT20126 promotes skin allograft survival by regulating the balance of Th1 and Th2 cytokine production.
- Source :
-
Experimental & molecular medicine [Exp Mol Med] 2007 Apr 30; Vol. 39 (2), pp. 230-8. - Publication Year :
- 2007
-
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-2(d)) to the dorsum of C57BL/6 (H-2(b)) 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.
- Subjects :
- Animals
Cell Line
Colchicine chemistry
Female
Gene Expression Regulation drug effects
Immunosuppression Therapy
Interleukin-1beta genetics
Interleukin-1beta metabolism
Lipopolysaccharides pharmacology
Lymphocyte Culture Test, Mixed
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Nitric Oxide biosynthesis
Nitric Oxide Synthase Type II genetics
Nitric Oxide Synthase Type II metabolism
Th1 Cells immunology
Th1 Cells metabolism
Th2 Cells immunology
Th2 Cells metabolism
Transplantation, Homologous
Tumor Necrosis Factor-alpha genetics
Tumor Necrosis Factor-alpha metabolism
Colchicine analogs & derivatives
Colchicine pharmacology
Cytokines biosynthesis
Graft Survival drug effects
Skin Transplantation immunology
Th1 Cells drug effects
Th2 Cells drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1226-3613
- Volume :
- 39
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Experimental & molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 17464185
- Full Text :
- https://doi.org/10.1038/emm.2007.26