| Regulation of human dendritic cells by a novel specific nuclear factor-kappaB inhibitor, dehydroxymethylepoxyquinomicin. | |
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MedLine Citation:
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PMID: 20573582 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Regulation of antigen-presenting cells (APC) is crucial in controlling allograft rejection. Dendritic cells (DC) are the most potent APC and must mature to present antigens to T-cell receptors. During DC maturation, nuclear factor-kappaB (NF-kappaB) is a key transcriptional factor. We synthesized dehydroxymethylepoxyquinomicin (DHMEQ), which specifically inhibits the final step of nuclear translocation of activated NF-kappaB proteins and examined its immunoregulatory effects on human monocyte-derived DC (Mo-DC). Regulatory Mo-DC were generated by pretreatment with DHMEQ before LPS stimulation, which were termed dl-DC. DHMEQ pretreatment (5 microg/ml) completely inhibited nuclear translocation of activated NF-kappaB. DHMEQ significantly inhibited DC production of proinflammatory cytokines (IL-6, TNF-alpha, and IL-12 p70) in a dose-dependent manner. IL-12 was most potently inhibited. However, IL-10 production by dl-DC was only moderately affected by DHMEQ. Although CD40 and the expression of HLA-DR (HLA-DR) expression on dl-DC was downregulated, CD80 and CD86 expression was moderately upregulated. Induction of T helper 1 cell responses was efficiently impaired by dl-DC. This confirmed that DHMEQ-treated Mo-DC exhibited immunoregulatory effects. These findings suggest that DHMEQ has potential as an immunosuppressive drug for human immune cells. |
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Authors:
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Kazunobu Shinoda; Ken Nakagawa; Takeo Kosaka; Nobuyuki Tanaka; Takahiro Maeda; Hidaka Kono; Ryuichi Mizuno; Eiji Kikuchi; Akira Miyajima; Kazuo Umezawa; Mototsugu Oya |
Publication Detail:
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Type: Journal Article Date: 2010-05-24 |
Journal Detail:
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Title: Human immunology Volume: 71 ISSN: 1879-1166 ISO Abbreviation: Hum. Immunol. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-19 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8010936 Medline TA: Hum Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 763-70 Citation Subset: IM |
Copyright Information:
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Copyright 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Urology, Keio University, School of Medicine, Shinjuku-ku, Tokyo, Japan. kshino49@yahoo.co.jp |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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