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Mycophenolate mofetil inhibits differentiation, maturation and allostimulatory function of human monocyte-derived dendritic cells

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2003
431.pdf (200.2Kb)
Authors
Colić, M
Stojić-Vukanić, Zorica
Pavlović, B
Jandrić, Dušan
Stefanoska, I
Article (Published version)
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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 / phenotype
Source:
Clinical and Experimental Immunology, 2003, 134, 1, 63-69
Publisher:
  • 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
[ Google Scholar ]
102
69
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/433
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
TY  - 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 . .

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