Effects of Vitamin E on FasL-induced Apoptotic Death of Dendritic Cells through PI3K Signaling
Main Article Content
This study addresses the effects of vitamin E (VitE) on the survival of mouse dendritic cells (DCs) and on underlying signaling molecules. To this end, mouse bone marrow cells were isolated and cultured to attain bone marrow-derived DCs (BMDCs). The cells were treated with FasL in the presence or absence of VitE. Western blotting and FACS analysis was performed to determine the expression of signaling molecules and their involvement in DC apoptosis. The FasL treatment resulted in activation of caspase 8 and an increased number of Annexin V+ cells; the effects were significantly suppressed when VitE was present in the cell culture. Importantly, the anti-apoptotic effects of VitE were abolished by using pharmacological inhibition of PI3K signaling with LY294002. The study results show that VitE inhibited FasL-mediated DC apoptosis through PI3K signaling, which is expected to facilitate the survival of DCs and promote the immune response against pathogens.
Caspase, dendritic cell, fas ligand, PI3K and vitamin E.
 J. Banchereau, R.M. Steinman, Dendritic cells and the control of immunity, Nature 392 (1998) 245-52.
 E. Ingulli, A. Mondino, A. Khoruts, M.K. Jenkins, In vivo detection of dendritic cell antigen presentation to CD4(+) T cells, J Exp Med 185 (1997) 2133-41.
 C. Yang, H.Z. Liu, Z.X. Fu, PEG-liposomal oxaliplatin induces apoptosis in human colorectal cancer cells via Fas/FasL and caspase-8, Cell Biol Int 36 (2012) 289-96.
 Q.G. Yan, J.G. Shi, F. Zhang, Q.T. Zhao, X.W. Pang, R. Chen, P.Z. Hu, Q.L. Li, Z. Wang, G.S. Huang, Overexpression of CYP2E1 enhances sensitivity of hepG2 cells to fas-mediated cytotoxicity, Cancer Biol Ther 7 (2008) 1280-7.
 A. Hamai, C. Richon, F. Meslin, F. Faure, A. Kauffmann, Y. Lecluse, A. Jalil, L. Larue, M.F. Avril, S. Chouaib, M. Mehrpour, Imatinib enhances human melanoma cell susceptibility to TRAIL-induced cell death: Relationship to Bcl-2 family and caspase activation, Oncogene 25 (2006) 7618-34.
 S. Lucken-Ardjomande, J.C. Martinou, Regulation of Bcl-2 proteins and of the permeability of the outer mitochondrial membrane, C R Biol 328 (2005) 616-31.
 M. Rescigno, V. Piguet, B. Valzasina, S. Lens, R. Zubler, L. French, V. Kindler, J. Tschopp, P. Ricciardi-Castagnoli, Fas engagement induces the maturation of dendritic cells (DCs), the release of interleukin (IL)-1beta, and the production of interferon gamma in the absence of IL-12 during DC-T cell cognate interaction: a new role for Fas ligand in inflammatory responses, J Exp Med 192 (2000) 1661-8.
 C. Qian, L. Qian, Y. Yu, H. An, Z. Guo, Y. Han, Y. Chen, Y. Bai, Q. Wang, X. Cao, Fas signal promotes the immunosuppressive function of regulatory dendritic cells via the ERK/beta-catenin pathway, J Biol Chem 288 (2013) 27825-35.
 L. Bo, S. Jiang, Y. Xie, H. Kan, W. Song, J. Zhao, Effect of Vitamin E and Omega-3 Fatty Acids on Protecting Ambient PM2.5-Induced Inflammatory Response and Oxidative Stress in Vascular Endothelial Cells, PLoS One 11 (2016) e0152216.
 K.S. Ahn, G. Sethi, K. Krishnan, B.B. Aggarwal, Gamma-tocotrienol inhibits nuclear factor-kappaB signaling pathway through inhibition of receptor-interacting protein and TAK1 leading to suppression of antiapoptotic gene products and potentiation of apoptosis, J Biol Chem 282 (2007) 809-20.
 E. Pierpaoli, V. Viola, F. Pilolli, M. Piroddi, F. Galli, M. Provinciali, Gamma- and delta-tocotrienols exert a more potent anticancer effect than alpha-tocopheryl succinate on breast cancer cell lines irrespective of HER-2/neu expression, Life Sci 86 (2010) 668-75.
 A.A. Albahrani, R.F. Greaves, Fat-Soluble Vitamins: Clinical Indications and Current Challenges for Chromatographic Measurement, Clin Biochem Rev 37 (2016) 27-47.
 E. Shumilina, N. Zahir, N.T. Xuan, F. Lang, Phosphoinositide 3-kinase dependent regulation of Kv channels in dendritic cells, Cell Physiol Biochem 20 (2007) 801-8.
 X. Jin, L. Song, X. Liu, M. Chen, Z. Li, L. Cheng, H. Ren, Protective efficacy of vitamins C and E on p,p'-DDT-induced cytotoxicity via the ROS-mediated mitochondrial pathway and NF-kappaB/FasL pathway, PLoS One 9 (2014) e113257.
 B.C. Richardson, N.D. Lalwani, K.J. Johnson, R.M. Marks, Fas ligation triggers apoptosis in macrophages but not endothelial cells, Eur J Immunol 24 (1994) 2640-5.
 J. Tschopp, M. Irmler, M. Thome, Inhibition of fas death signals by FLIPs, Curr Opin Immunol 10 (1998) 552-8.
 J. Chung, Y.O. Yoon, J.S. Lee, T.K. Ha, S.M. Ryu, K.H. Kim, M.H. Jeong, T.R. Yoon, H.K. Kim, Inulin induces dendritic cells apoptosis through the caspase-dependent pathway and mitochondrial dysfunction, Biol Pharm Bull 34 (2011) 495-500.
 S. Kreuz, D. Siegmund, J.J. Rumpf, D. Samel, M. Leverkus, O. Janssen, G. Hacker, O. Dittrich-Breiholz, M. Kracht, P. Scheurich, H. Wajant, NFkappaB activation by Fas is mediated through FADD, caspase-8, and RIP and is inhibited by FLIP, J Cell Biol 166 (2004) 369-80.
 S. Buonocore, S. Van Meirvenne, F.X. Demoor, F. Paulart, K. Thielemans, M. Goldman, V. Flamand, Dendritic cells transduced with viral interleukin 10 or Fas ligand: no evidence for induction of allotolerance in vivo, Transplantation 73 (2002) S27-30.
 D. Ashany, A. Savir, N. Bhardwaj, K.B. Elkon, Dendritic cells are resistant to apoptosis through the Fas (CD95/APO-1) pathway, J Immunol 163 (1999) 5303-11.
 D. Ashany, X. Song, E. Lacy, J. Nikolic-Zugic, S.M. Friedman, K.B. Elkon, Th1 CD4+ lymphocytes delete activated macrophages through the Fas/APO-1 antigen pathway, Proc Natl Acad Sci U S A 92 (1995) 11225-9.
 S. Qi, W. Fu, C. Wang, C. Liu, C. Quan, A. Kourouma, M. Yan, T. Yu, P. Duan, K. Yang, BPA-induced apoptosis of rat Sertoli cells through Fas/FasL and JNKs/p38 MAPK pathways, Reprod Toxicol 50 (2014) 108-16.
 L.P. Eberl, G. Egidy, F. Pinet, L. Juillerat-Jeanneret, Endothelin receptor blockade potentiates FasL-induced apoptosis in colon carcinoma cells via the protein kinase C-pathway, J Cardiovasc Pharmacol 36 (2000) S354-6.
 N.T. Xuan, P.T. Trang, N. Van Phong, N.L. Toan, D.M. Trung, N.D. Bac, V.L. Nguyen, N.H. Hoang, N. Van Hai, Klotho sensitive regulation of dendritic cell functions by vitamin E, Biol Res 49 (2016) 45-54.
 M. Baskiewicz-Masiuk, B. Machalinski, The role of the STAT5 proteins in the proliferation and apoptosis of the CML and AML cells, Eur J Haematol 72 (2004) 420-9.