Exp Mol Med.
2007 Apr;39(2):230-238.
Colchicine-derived compound CT20126 promotes skin allograft survival by regulating the balance of Th1 and Th2 cytokine production
- Affiliations
-
- 1Vascular System Research Center Korea. ymkim@kangwon.ac.kr
- 2Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
- 3Department of Orthopaedic Surgery, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
- 4Department of Biochemistry, College of Medicine, Yonsei University Seoul 120-749, Korea.
- 5Team of Biotech and Drug Development Chem-Tech Research Incorporation, Suwon University, Hwaseong 445-743, Korea.
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.
Keyword
MeSH Terms
-
Animals
Cell Line
Colchicine/*analogs & derivatives/chemistry/*pharmacology
Cytokines/*biosynthesis
Female
Gene Expression Regulation/drug effects
Graft Survival/*drug effects
Immunosuppression
Interleukin-1beta/genetics/metabolism
Lipopolysaccharides/pharmacology
Lymphocyte Culture Test, Mixed
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Nitric Oxide/biosynthesis
Nitric Oxide Synthase Type II/genetics/metabolism
Skin Transplantation/*immunology
Th1 Cells/*drug effects/immunology/metabolism
Th2 Cells/*drug effects/immunology/metabolism
Transplantation, Homologous
Tumor Necrosis Factor-alpha/genetics/metabolism
- Full Text Links
-
- Actions
-
Cited
- CITED
-
- Close
- Share
-
- Similar articles
-
- Th1/Th2 Cytokine Production in Patients with Chronic Hepatitis C Virus Infection
- Concurrent Impairment of Th1 and Th2 Response in Thermal Injury
- Cytokines in Chronic Hepatitis B and C Virus Infections
- 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (EC-18) Modulates Th2 Immunity through Attenuation of IL-4 Expression
- Production of interferon-gamma and interleukin-4 by splenocytes in mice infected with Paragonimus westermani
