2-Chlorodeoxyadenosine (cladribine) induces apoptosis in human monocyte-derived dendritic cells

Autor:	Karelle Bénardais, Elke Voss, Martin Stangel, Viktoria Gudi, Chittappen K. Prajeeth, Vikramjeet Singh
Rok vydání:	2013
Předmět:	Multiple Sclerosis medicine.medical_treatment Immunology Apoptosis Monocytes chemistry.chemical_compound Immune system medicine Chlorodeoxyadenosine Humans Immunology and Allergy Cladribine Cells Cultured Caspase Membrane Potential Mitochondrial Leukemia Hairy Cell biology Caspase 3 Cell Differentiation Dendritic Cells Original Articles Phosphatidylserine Caspase 9 Immunosuppressive drug chemistry biology.protein DNA fragmentation Tumor Suppressor Protein p53 Immunosuppressive Agents DNA Damage medicine.drug
Zdroj:	Clinical and Experimental Immunology. 173:288-297
ISSN:	1365-2249 0009-9104
Popis:	Summary 2-Chlorodeoxyadenosine (cladribine, CdA) is an immunosuppressive drug that is licensed to treat hairy cell leukaemia, and has been shown recently to have beneficial effects in patients with multiple sclerosis (MS). The therapeutic effects of CdA have been suggested to be mediated partly through its potent toxicity towards lymphocytes. However, the effects of CdA on other immune cells are poorly understood. In the present study, we investigated the effects of CdA on the induction of apoptosis in human monocytes, monocyte-derived immature (ImDC) and mature (mDC) dendritic cells. Treatment of monocytes with CdA strongly induced apoptosis after 24 h, while apoptosis induction in DC was evident after 72 h. Furthermore, CdA treatment strongly induced caspase-3 and caspase-9 in monocytes, whereas activation of caspases was undetected in DC. The mitochondrial membrane potential in DC was reduced significantly after CdA treatment. DNA hypodiploid assessment showed fragmented nuclei in DC after CdA treatment together with activation of p53 protein. These results revealed that CdA induces caspase-independent apoptosis in DC and suggest cell type specific effects of CdA. This mechanism may contribute to the effect of CdA in autoimmune diseases.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1f2209696b932e612acfee626a12d976 https://doi.org/10.1111/cei.12109 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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