PMID- 27881156 OWN - NLM STAT- MEDLINE DCOM- 20170413 LR - 20211203 IS - 0717-6287 (Electronic) IS - 0716-9760 (Print) IS - 0716-9760 (Linking) VI - 49 IP - 1 DP - 2016 Nov 24 TI - Klotho sensitive regulation of dendritic cell functions by vitamin E. PG - 45 LID - 45 AB - BACKGROUND: Dendritic cells (DCs) are the most potent professional antigen-presenting cells for naive T cells to link innate and acquired immunity. Klotho, an anti-aging protein, participates in the regulation of Ca(2+) dependent migration in DCs. Vitamin E (VitE) is an essential antioxidant to protect cells from damage and elicits its inhibitory effects on NF-kappaB-mediated inflammatory response. However, the roles of VitE on mouse DC functions and the contribution of klotho to those effects both are unknown. The present study explored the effects of VitE on klotho expression, maturation, ROS production and migration in DCs. METHODS: The mouse bone marrow cells were isolated and cultured with GM-CSF to attain bone marrow-derived DCs (BMDCs). Cells were stimulated with LPS (100 ng/ml) in the presence or absence of VitE (500 microM). RT-PCR and immunoprecipitation methods were employed to determine klotho expression, ELISA to determine cytokine release, flow cytometry to analyze number of CD86(+)CD11c(+) cells, the intracellular expression of cytokines and reactive oxygen species (ROS) production and a transwell migration assay to trace migration. RESULTS: Klotho transcript level and this hormone secretion in DC supernatant were enhanced by VitE treatment and further increased in the presence of NF-kappaB inhibitor Bay 11-7082 (10 microM). Moreover, VitE treatment inhibited IL-12p70 protein expression of, ROS accumulation in and CCL21-dependent migration of LPS-triggered mature DCs, these effects were reversed following klotho silencing. CONCLUSION: The up-regulation of klotho by VitE could contribute to the inhibitory effects of VitE on NF-kappaB-mediated DC functional maturation. The events might contribute to immunotherapeutic effect of VitE on the pathophysiology of klotho-related disease. FAU - Xuan, Nguyen Thi AU - Xuan NT AD - Institute of Genome Research, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam. xuannt@igr.ac.vn. FAU - Trang, Phi Thi Thu AU - Trang PT AD - Institute of Genome Research, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam. FAU - Van Phong, Nguyen AU - Van Phong N AD - Institute of Genome Research, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam. FAU - Toan, Nguyen Linh AU - Toan NL AD - Department of Pathophysiology, Vietnam Military Medical University, Ha Dong, Hanoi, Vietnam. FAU - Trung, Do Minh AU - Trung DM AD - Department of Protein-Toxic-Cells, Biomedical & Pharmaceutical Applied Research Center, Vietnam Military Medical University, Ha Dong, Hanoi, Vietnam. FAU - Bac, Nguyen Duy AU - Bac ND AD - Vietnam Military Medical University, Ha Dong, Hanoi, Vietnam. FAU - Nguyen, Viet Linh AU - Nguyen VL AD - Institute of Biotechnology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam. FAU - Hoang, Nguyen Huy AU - Hoang NH AD - Institute of Genome Research, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam. FAU - Van Hai, Nong AU - Van Hai N AD - Institute of Genome Research, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam. LA - eng PT - Evaluation Study PT - Journal Article DEP - 20161124 PL - England TA - Biol Res JT - Biological research JID - 9308271 RN - 0 (IkappaBNS protein, mouse) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Lipopolysaccharides) RN - 0 (Proteins) RN - 0 (Reactive Oxygen Species) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Vitamins) RN - 1406-18-4 (Vitamin E) RN - 187348-17-0 (Interleukin-12) RN - EC 3.2.1.31 (Glucuronidase) RN - EC 3.2.1.31 (Klotho Proteins) SB - IM MH - Analysis of Variance MH - Animals MH - Bone Marrow Cells/cytology MH - Cell Movement/drug effects MH - Dendritic Cells/*drug effects/physiology MH - Enzyme-Linked Immunosorbent Assay MH - Flow Cytometry MH - Glucuronidase/*drug effects/physiology MH - Immunoblotting MH - Interleukin-12/analysis MH - Intracellular Signaling Peptides and Proteins MH - Klotho Proteins MH - Lipopolysaccharides MH - Mice, Inbred BALB C MH - Proteins/analysis/drug effects MH - Reactive Oxygen Species/metabolism MH - Real-Time Polymerase Chain Reaction MH - Reproducibility of Results MH - Time Factors MH - Tumor Necrosis Factor-alpha/analysis MH - Up-Regulation MH - Vitamin E/*pharmacology MH - Vitamins/*pharmacology PMC - PMC5121936 OTO - NOTNLM OT - Dendritic cells OT - Klotho OT - LPS OT - Migration OT - ROS OT - Vitamin E EDAT- 2016/11/25 06:00 MHDA- 2017/04/14 06:00 PMCR- 2016/11/24 CRDT- 2016/11/25 06:00 PHST- 2016/08/09 00:00 [received] PHST- 2016/11/17 00:00 [accepted] PHST- 2016/11/25 06:00 [entrez] PHST- 2016/11/25 06:00 [pubmed] PHST- 2017/04/14 06:00 [medline] PHST- 2016/11/24 00:00 [pmc-release] AID - 10.1186/s40659-016-0105-4 [pii] AID - 105 [pii] AID - 10.1186/s40659-016-0105-4 [doi] PST - epublish SO - Biol Res. 2016 Nov 24;49(1):45. doi: 10.1186/s40659-016-0105-4.