Mycophenolate mofetil inhibits differentiation, maturation and allostimulatory function of human monocyte-derived dendritic cells
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 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.
Keywords:
alloreactivity / cytokine production / endocytosis / human dendritic cells / mycophenolate mofetil / phenotypeSource:
Clinical and Experimental Immunology, 2003, 134, 1, 63-69Publisher:
- 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
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Institution/Community
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 . .