| Midostaurin (PKC412) modulates differentiation and maturation of human myeloid dendritic cells. | |
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MedLine Citation:
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PMID: 20685248 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Midostaurin, a tyrosine kinase inhibitor, has been shown efficacy against acute myeloid leukemia and various other malignancies in clinical trials. Prior studies indicate midostaurin affects the function of immune cells such as lymphocytes and macrophages. To understand the effect of midostaurin on human myeloid dendritic cells (DCs), we conducted an ex vivo study using immature DCs differentiated from CD14(+) monocytes and further maturated using lipopolysaccharide. Addition of midostaurin to a culture of starting CD14(+) monocytes markedly and dose-dependently reduced DC recovery. Mature DCs differentiating in the presence of midostaurin had fewer, shorter cell projections than those differentiating in the absence of midostaurin. Changes in morphological features characteristic of apoptotic cells were also evident. Moreover, midostaurin affected DC differentiation and maturation patterns; CD83 expression levels decreased, whereas CD14 and CD80 expressions increased. Additionally, DCs derived in the presence of midostaurin possessed a lower endocytotic capacity and less allostimulatory activity on naive CD4(+)CD45(+)RA(+) T cell proliferation than those derived in its absence, suggesting that midostaurin redirects DC differentiation toward a less mature stage and that this effect is not solely due to its cytotoxicity. Whether this effect underlies immune suppression or tolerance to disease treatments with unwanted immune reactions needs further evaluation. |
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Authors:
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Yu-Chuen Huang; Hui-Ru Shieh; Yu-Jen Chen |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-05-26 |
Journal Detail:
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Title: Toxicology in vitro : an international journal published in association with BIBRA Volume: 24 ISSN: 1879-3177 ISO Abbreviation: Toxicol In Vitro Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-31 Completed Date: 2010-12-14 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8712158 Medline TA: Toxicol In Vitro Country: England |
Other Details:
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Languages: eng Pagination: 1705-10 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antigens, CD
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metabolism Antineoplastic Agents / pharmacology* Apoptosis / drug effects Biological Markers / metabolism Bone Marrow Cells / cytology* Cell Differentiation / drug effects Cell Proliferation / drug effects Cells, Cultured Dendritic Cells / drug effects*, immunology, pathology Endocytosis / drug effects Humans Lipopolysaccharides / pharmacology Protein Kinase C / antagonists & inhibitors* Staurosporine / analogs & derivatives*, pharmacology Transport Vesicles / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD; 0/Antineoplastic Agents; 0/Biological Markers; 0/Lipopolysaccharides; 120685-11-2/4'-N-benzoylstaurosporine; 62996-74-1/Staurosporine; EC 2.7.11.13/Protein Kinase C |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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