Differentiation and function of human monocyte-derived dendritic cells under the influence of leflunomide
2011
Authors
Stojić-Vukanić, ZoricaČolić, Miodrag
Backović, A.
Antić-Stanković, Jelena
Bufan, Biljana
Dimitrijević, M.
Article (Published version)
Metadata
Show full item recordAbstract
Leflunomide is an immunosuppressive drug effective in experimental models of transplantation and autoimmune diseases and in the treatment of active rheumatoid arthritis (RA). Having in mind that it has been shown that some other immunosuppressive drugs (glucocorticoids, mycophenolate mofetil, sirolimus etc.) impair dendritic cell (DC) phenotype and function, we investigated the effect of A77 1726, an active metabolite of leflunomide, on the differentiation and function of human monocyte-derived dendritic cells (MDDC) in vitro. Immature MDDC were generated by cultivating monocytes in medium supplemented with GM-CSF and IL-4. To induce maturation, immature MDDC were cultured for 2 additional days with LPS. A77 1726 (100 μM) was added at the beginning of cultivation. Flow cytometric analysis showed that MDDC differentiated in the presence of A77 1726 exhibited an altered phenotype, with a down-regulated surface expression of CD80, CD86, CD54 and CD40 molecules. Furthermore, the continuous... presence of A77 1726 during differentiation and maturation prevented successful maturation, judging by the decreased expression of maturation marker CD83, costimulatory and adhesive molecules on A77 1726-treated mature MDDC. In addition, A77 1726-pretreated MDDC exhibited a poor stimulatory capacity of the allogeneic T cells and a low production of IL-10 and IL-18. These data suggest that leflunomide impairs the differentiation, maturation and function of human MDDC in vitro, which is an additional mechanism of its immunosuppressive effect.
Keywords:
Alloreactivity / cytokine production / human dendritic cells / leflunomide / phenotypeSource:
Archives of Biological Sciences, 2011, 63, 2, 353-364Publisher:
- Srpsko biološko društvo, Beograd, i dr.
DOI: 10.2298/ABS1102353S
ISSN: 0354-4664
WoS: 000291130000008
Scopus: 2-s2.0-79961187950
Collections
Institution/Community
PharmacyTY - JOUR AU - Stojić-Vukanić, Zorica AU - Čolić, Miodrag AU - Backović, A. AU - Antić-Stanković, Jelena AU - Bufan, Biljana AU - Dimitrijević, M. PY - 2011 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1580 AB - Leflunomide is an immunosuppressive drug effective in experimental models of transplantation and autoimmune diseases and in the treatment of active rheumatoid arthritis (RA). Having in mind that it has been shown that some other immunosuppressive drugs (glucocorticoids, mycophenolate mofetil, sirolimus etc.) impair dendritic cell (DC) phenotype and function, we investigated the effect of A77 1726, an active metabolite of leflunomide, on the differentiation and function of human monocyte-derived dendritic cells (MDDC) in vitro. Immature MDDC were generated by cultivating monocytes in medium supplemented with GM-CSF and IL-4. To induce maturation, immature MDDC were cultured for 2 additional days with LPS. A77 1726 (100 μM) was added at the beginning of cultivation. Flow cytometric analysis showed that MDDC differentiated in the presence of A77 1726 exhibited an altered phenotype, with a down-regulated surface expression of CD80, CD86, CD54 and CD40 molecules. Furthermore, the continuous presence of A77 1726 during differentiation and maturation prevented successful maturation, judging by the decreased expression of maturation marker CD83, costimulatory and adhesive molecules on A77 1726-treated mature MDDC. In addition, A77 1726-pretreated MDDC exhibited a poor stimulatory capacity of the allogeneic T cells and a low production of IL-10 and IL-18. These data suggest that leflunomide impairs the differentiation, maturation and function of human MDDC in vitro, which is an additional mechanism of its immunosuppressive effect. PB - Srpsko biološko društvo, Beograd, i dr. T2 - Archives of Biological Sciences T1 - Differentiation and function of human monocyte-derived dendritic cells under the influence of leflunomide VL - 63 IS - 2 SP - 353 EP - 364 DO - 10.2298/ABS1102353S ER -
@article{ author = "Stojić-Vukanić, Zorica and Čolić, Miodrag and Backović, A. and Antić-Stanković, Jelena and Bufan, Biljana and Dimitrijević, M.", year = "2011", abstract = "Leflunomide is an immunosuppressive drug effective in experimental models of transplantation and autoimmune diseases and in the treatment of active rheumatoid arthritis (RA). Having in mind that it has been shown that some other immunosuppressive drugs (glucocorticoids, mycophenolate mofetil, sirolimus etc.) impair dendritic cell (DC) phenotype and function, we investigated the effect of A77 1726, an active metabolite of leflunomide, on the differentiation and function of human monocyte-derived dendritic cells (MDDC) in vitro. Immature MDDC were generated by cultivating monocytes in medium supplemented with GM-CSF and IL-4. To induce maturation, immature MDDC were cultured for 2 additional days with LPS. A77 1726 (100 μM) was added at the beginning of cultivation. Flow cytometric analysis showed that MDDC differentiated in the presence of A77 1726 exhibited an altered phenotype, with a down-regulated surface expression of CD80, CD86, CD54 and CD40 molecules. Furthermore, the continuous presence of A77 1726 during differentiation and maturation prevented successful maturation, judging by the decreased expression of maturation marker CD83, costimulatory and adhesive molecules on A77 1726-treated mature MDDC. In addition, A77 1726-pretreated MDDC exhibited a poor stimulatory capacity of the allogeneic T cells and a low production of IL-10 and IL-18. These data suggest that leflunomide impairs the differentiation, maturation and function of human MDDC in vitro, which is an additional mechanism of its immunosuppressive effect.", publisher = "Srpsko biološko društvo, Beograd, i dr.", journal = "Archives of Biological Sciences", title = "Differentiation and function of human monocyte-derived dendritic cells under the influence of leflunomide", volume = "63", number = "2", pages = "353-364", doi = "10.2298/ABS1102353S" }
Stojić-Vukanić, Z., Čolić, M., Backović, A., Antić-Stanković, J., Bufan, B.,& Dimitrijević, M.. (2011). Differentiation and function of human monocyte-derived dendritic cells under the influence of leflunomide. in Archives of Biological Sciences Srpsko biološko društvo, Beograd, i dr.., 63(2), 353-364. https://doi.org/10.2298/ABS1102353S
Stojić-Vukanić Z, Čolić M, Backović A, Antić-Stanković J, Bufan B, Dimitrijević M. Differentiation and function of human monocyte-derived dendritic cells under the influence of leflunomide. in Archives of Biological Sciences. 2011;63(2):353-364. doi:10.2298/ABS1102353S .
Stojić-Vukanić, Zorica, Čolić, Miodrag, Backović, A., Antić-Stanković, Jelena, Bufan, Biljana, Dimitrijević, M., "Differentiation and function of human monocyte-derived dendritic cells under the influence of leflunomide" in Archives of Biological Sciences, 63, no. 2 (2011):353-364, https://doi.org/10.2298/ABS1102353S . .