title: Venlafaxine inhibits the development and differentiation of dendritic cells through the regulation of P-glycoprotein.
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 (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: Department of Biology, College of Natural Science, Chosun University, Gwangju 501-759, South Korea.
authors: Jun Sik
authors: JS
authors: Lee
authors: In Duk
authors: ID
authors: Jung
authors: Chang-Min
authors: CM
authors: Lee
authors: Kyung Tae
authors: KT
authors: Noh
authors: Jin Wook
authors: JW
authors: Park
authors: Kwang Hee
authors: KH
authors: Son
authors: Deok Rim
authors: DR
authors: Heo
authors: Yong Kyoo
authors: YK
authors: Shin
authors: Daejin
authors: D
authors: Kim
authors: Yeong-Min
authors: YM
authors: Park