Klotho sensitive regulation of dendritic cell functions by vitamin E

Abstract

BackgroundDendritic 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 Ca2+ dependent migration in DCs. Vitamin E (VitE) is an essential antioxidant to protect cells from damage and elicits its inhibitory effects on NF-κB-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.MethodsThe 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 µM). 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.ResultsKlotho transcript level and this hormone secretion in DC supernatant were enhanced by VitE treatment and further increased in the presence of NF-κB inhibitor Bay 11-7082 (10 µM). 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.ConclusionThe up-regulation of klotho by VitE could contribute to the inhibitory effects of VitE on NF-κB-mediated DC functional maturation. The events might contribute to immunotherapeutic effect of VitE on the pathophysiology of klotho-related disease.

The Role of Vitamin E in Immunity

“…These effects of vitamin E on BMDCs were partly dependent on Klotho expression. Vitamin E treatment on BMDCs resulted in higher Klotho transcript and protein levels, and silencing of Klotho by transfection of Klotho siRNA abolished the inhibitory effects of vitamin E on IL-12p70 production, number of ROS-positive cells, and DC migration [ 76 ]. Klotho is a membrane protein that has been shown to mediate calcium transport into the cells; regulate intracellular signaling pathways such as p53/p21, cyclin adenosine monophosphate (cAMP), PKC, and Wnt; and inhibit the NF-κB pathway [ 77 ].…”

Regulation of p38MAPK‐mediated dendritic cell functions by the deubiquitylase otubain 1

“…Recent study shows the role of OTUB1 in promoting the migration of cancer cells . Mature DCs express the high level of CCR7 receptor, thus they are induced to migrate toward CCR7 ligands, such as CCL21, which is expressed in LNs . In this study, treatment of DCs with LPS enhances the migration of DCs , which was remained unaltered when the cells were transfected with OTUB1 siRNA (Figure ), indicating that the migration of DCs was not dependent on the presence of OTUB1.…”

“…Of note, these cells are derived from different sources and genes involved in the regulation of their migration capacity are distinct from each other. Silencing of OTUB1 in cancer cells inhibits migration through decreased expression of some extracellular matrix degradation‐related proteins, such as matrix metallopeptidase (MMP)2 and MMP9 and DC migration is under the control of chemokine receptors including C‐C chemokine receptor (CCR)7 and CCR9 and their corresponding ligands CCL19 and CCL21, respectively .…”

“…The methods used in this study were previously described elsewhere . BALB/c mice were anesthetized with isoflurane gas and bone marrow cells were flushed out of the cavities from the femur and tibia with PBS.…”

A Rapid Advice Guideline for the Prevention of Novel Coronavirus Through Nutritional Intervention

“…Similarly, vitamin E exists in high concentrations in immune cells, which further protects these cells from any oxidative injury because of their high metabolic activity and PUFA contents [34,35]. It has also been known that vitamin E regulates the growth and functions of dendritic cells, which are essential for interlacing innate and adaptive immune systems to manage immune response in the body [36,37]. Vitamin E has been displayed its positive effect in improving T cell immune synapse development and begin T cell activation signals [38].…”