Mycophenolate mofetil inhibits differentiation, maturation and allostimulatory function of human monocyte-derived dendritic cells
Апстракт
We have studied the effect of mycophenolate mofetil (MMF), a new drug used in prevention of transplant rejection, on differentiation, maturation and allostimulatory activity of human monocyte-derived dendritic cells (MDDC). MDDC were generated in vitro with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-4 in the presence or absence of MMF. MMF reduced the number of immature MDDC in culture, dose-dependently, by inducing apoptosis and inhibited their stimulatory activity on allogeneic lymphocytes. These changes correlated with down-regulation of costimulatory and adhesion molecules such as CD40, CD54, CD80 and CD86. No differences were observed in mannose receptor (MR)-mediated endocytosis, measured by the uptake of fluorescein isothiocyanate (FITC)-dextran. MDDC differentiated in the presence of MMF showed significantly reduced maturation upon stimulation with lipopolysaccharide, as judged by lower expresson of CD83 and co-stimulatory molecules, lower pr...oduction of tumour necrosis factor (TNF)-alpha, IL-10, IL-12 and IL-18 as well as lower stimulation of alloreactive T cells including naive CD4(+) CD45RA(+)T cells. In contrast, MDDC matured in the presence of MMF showed a more marked decrease in the FITC-dextran uptake than mature MDDC cultivated without MMF and the phenomenon correlated with down-regulation of the MR expression. These results suggest that MMF impairs differentiation, maturation and function of human MDDC in vitro, which is an additional mechanism of its immunosuppressive effect.
Кључне речи:
alloreactivity / cytokine production / endocytosis / human dendritic cells / mycophenolate mofetil / phenotypeИзвор:
Clinical and Experimental Immunology, 2003, 134, 1, 63-69Издавач:
- Blackwell Publishing Ltd, Oxford
DOI: 10.1046/j.1365-2249.2003.02269.x
ISSN: 0009-9104
PubMed: 12974756
WoS: 000185345200011
Scopus: 2-s2.0-19244387277
Институција/група
PharmacyTY - JOUR AU - Colić, M AU - Stojić-Vukanić, Zorica AU - Pavlović, B AU - Jandrić, Dušan AU - Stefanoska, I PY - 2003 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/433 AB - We have studied the effect of mycophenolate mofetil (MMF), a new drug used in prevention of transplant rejection, on differentiation, maturation and allostimulatory activity of human monocyte-derived dendritic cells (MDDC). MDDC were generated in vitro with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-4 in the presence or absence of MMF. MMF reduced the number of immature MDDC in culture, dose-dependently, by inducing apoptosis and inhibited their stimulatory activity on allogeneic lymphocytes. These changes correlated with down-regulation of costimulatory and adhesion molecules such as CD40, CD54, CD80 and CD86. No differences were observed in mannose receptor (MR)-mediated endocytosis, measured by the uptake of fluorescein isothiocyanate (FITC)-dextran. MDDC differentiated in the presence of MMF showed significantly reduced maturation upon stimulation with lipopolysaccharide, as judged by lower expresson of CD83 and co-stimulatory molecules, lower production of tumour necrosis factor (TNF)-alpha, IL-10, IL-12 and IL-18 as well as lower stimulation of alloreactive T cells including naive CD4(+) CD45RA(+)T cells. In contrast, MDDC matured in the presence of MMF showed a more marked decrease in the FITC-dextran uptake than mature MDDC cultivated without MMF and the phenomenon correlated with down-regulation of the MR expression. These results suggest that MMF impairs differentiation, maturation and function of human MDDC in vitro, which is an additional mechanism of its immunosuppressive effect. PB - Blackwell Publishing Ltd, Oxford T2 - Clinical and Experimental Immunology T1 - Mycophenolate mofetil inhibits differentiation, maturation and allostimulatory function of human monocyte-derived dendritic cells VL - 134 IS - 1 SP - 63 EP - 69 DO - 10.1046/j.1365-2249.2003.02269.x ER -
@article{ author = "Colić, M and Stojić-Vukanić, Zorica and Pavlović, B and Jandrić, Dušan and Stefanoska, I", year = "2003", abstract = "We have studied the effect of mycophenolate mofetil (MMF), a new drug used in prevention of transplant rejection, on differentiation, maturation and allostimulatory activity of human monocyte-derived dendritic cells (MDDC). MDDC were generated in vitro with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-4 in the presence or absence of MMF. MMF reduced the number of immature MDDC in culture, dose-dependently, by inducing apoptosis and inhibited their stimulatory activity on allogeneic lymphocytes. These changes correlated with down-regulation of costimulatory and adhesion molecules such as CD40, CD54, CD80 and CD86. No differences were observed in mannose receptor (MR)-mediated endocytosis, measured by the uptake of fluorescein isothiocyanate (FITC)-dextran. MDDC differentiated in the presence of MMF showed significantly reduced maturation upon stimulation with lipopolysaccharide, as judged by lower expresson of CD83 and co-stimulatory molecules, lower production of tumour necrosis factor (TNF)-alpha, IL-10, IL-12 and IL-18 as well as lower stimulation of alloreactive T cells including naive CD4(+) CD45RA(+)T cells. In contrast, MDDC matured in the presence of MMF showed a more marked decrease in the FITC-dextran uptake than mature MDDC cultivated without MMF and the phenomenon correlated with down-regulation of the MR expression. These results suggest that MMF impairs differentiation, maturation and function of human MDDC in vitro, which is an additional mechanism of its immunosuppressive effect.", publisher = "Blackwell Publishing Ltd, Oxford", journal = "Clinical and Experimental Immunology", title = "Mycophenolate mofetil inhibits differentiation, maturation and allostimulatory function of human monocyte-derived dendritic cells", volume = "134", number = "1", pages = "63-69", doi = "10.1046/j.1365-2249.2003.02269.x" }
Colić, M., Stojić-Vukanić, Z., Pavlović, B., Jandrić, D.,& Stefanoska, I.. (2003). Mycophenolate mofetil inhibits differentiation, maturation and allostimulatory function of human monocyte-derived dendritic cells. in Clinical and Experimental Immunology Blackwell Publishing Ltd, Oxford., 134(1), 63-69. https://doi.org/10.1046/j.1365-2249.2003.02269.x
Colić M, Stojić-Vukanić Z, Pavlović B, Jandrić D, Stefanoska I. Mycophenolate mofetil inhibits differentiation, maturation and allostimulatory function of human monocyte-derived dendritic cells. in Clinical and Experimental Immunology. 2003;134(1):63-69. doi:10.1046/j.1365-2249.2003.02269.x .
Colić, M, Stojić-Vukanić, Zorica, Pavlović, B, Jandrić, Dušan, Stefanoska, I, "Mycophenolate mofetil inhibits differentiation, maturation and allostimulatory function of human monocyte-derived dendritic cells" in Clinical and Experimental Immunology, 134, no. 1 (2003):63-69, https://doi.org/10.1046/j.1365-2249.2003.02269.x . .