Venlafaxine inhibits the development and differentiation of dendritic cells through the regulation of p-glycoproteinopen access
- Authors
- Lee, Jun Sik; Jung, In Duk; Lee, Chang-Min; Noh, Kyung Tae; Park, Jin Wook; Son, Kwang Hee; Heo, Deok Rim; Shin, Yong Kyoo; Kim, Daejin; Park, Yeong-Min
- Issue Date
- Sep-2011
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- Dendritic cells; P-glycoprotein; Development; Differentiation; Cytokines
- Citation
- INTERNATIONAL IMMUNOPHARMACOLOGY, v.11, no.9, pp 1348 - 1357
- Pages
- 10
- Journal Title
- INTERNATIONAL IMMUNOPHARMACOLOGY
- Volume
- 11
- Number
- 9
- Start Page
- 1348
- End Page
- 1357
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/21292
- DOI
- 10.1016/j.intimp.2011.04.019
- ISSN
- 1567-5769
1878-1705
- Abstract
- 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 (VEX) 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-gamma, 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. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved.
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