Document Detail


Venlafaxine inhibits the development and differentiation of dendritic cells through the regulation of p-glycoprotein.
MedLine Citation:
PMID:  21605706     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Dendritic cells (DC) are professional antigen-presenting cells that have the ability to detect infectious materials; antigens to T lymphocytes, and serve as a bridge between innate and adaptive immunities. DC express the ATP-binding cassette transporters P-glycoprotein (P-gp). P-gp is a 170-kDa transmembrane protein encoded by the mdr-1 gene, a member of highly conserved superfamily of ATP-binding cassette transport proteins. Functionally, P-gp transporters have been described to be required for efficient DC and T cell migration. We report for the first time, at the best of our knowledge, P-gp is also required for DC development and differentiation in mouse bone marrow-derived DC. In this study, we found that an mdr-1 gene and P-gp protein level was increased during DC development and LPS-induced maturation. Moreover, the activity of P-gp was increased LPS-induced DC maturation. Next, we have attempted to determine whether the modulation of P-gp regulates surface molecules expression and cytokine production in DC. Specifically, down-regulation of P-gp by Venlafaxine (VLX) inhibits the differentiation of DC and cytokine production, such as IL-1, IL-10, and IL-12 during DC maturation. Moreover, the P-gp-decreased DC by VLX was displayed impaired induction of T cell polarizations, proliferation, and cytokine production, including IFN-γ, IL-4, and IL-2. Taken together, these findings also broaden current perspective concerning our understanding of the immunopharmacological functions of VLX and the development of therapeutic adjuvants for the treatment of DC-related acute and chronic diseases.
Authors:
Jun Sik Lee; In Duk Jung; Chang-Min Lee; Kyung Tae Noh; Jin Wook Park; Kwang Hee Son; Deok Rim Heo; Yong Kyoo Shin; Daejin Kim; Yeong-Min Park
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-20
Journal Detail:
Title:  International immunopharmacology     Volume:  -     ISSN:  1878-1705     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100965259     Medline TA:  Int Immunopharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.
Affiliation:
Department of Biology, College of Natural Science, Chosun University, Gwangju 501-759, South Korea.
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