Study of calcitriol anti-aging effects on human natural killer cells <i>in vitro</i>

Vitamin D is widely considered to have a regulatory effect on the immune system. Some clinical investigations have shown that the demand for vitamin D increases with age. Calcitriol is the biologically active form of vitamin D. However, its effect on human natural killer (NK) cells remains unclear. Therefore, in this study, we investigated the anti-aging and immunomodulatory effects of calcitriol on NK cells using a series of immunological methods to explore its important role in innate immunity. We found that calcitriol reversed the expression of aging-related biomarkers in NK cells and inhibited their expansion by maintaining these cells in the G1 phase, without any apoptosis and exhaustion. Calcitriol repressed the release of inflammation-related cytokines, such as interleukin-5 (IL-5), interleukin-13 (IL-13), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α). The degranulation of NK cells was downregulated by calcitriol when these cells were co-cultured with K562 tumor cells. We also found that calcitriol upregulated the aging-related sirtuin 1- protein/kinase R-like endoplasmic reticulum kinase (SIRT1/pERK) pathway and SIRT1-deltaExon8 (SIRT1-∆Exon8) expression by activating the vitamin D receptor (VDR). Moreover, calcitriol could be a potential negative regulator of NK cell apoptosis and mitochondrial inactivation which caused by oxidative stress. Thus, calcitriol exhibits anti-aging effects on human NK cells <i>in vitro</i> by activating the SIRT1-PERK axis and resisting oxidative senescence.

维生素D（Vitamin D）被广泛认为对免疫系统具有调节作用。多项临床研究表明，机体对维生素D的需求随年龄增长而升高。骨化三醇（calcitriol）是维生素D的生物活性形式，但其对人自然杀伤（NK）细胞（natural killer (NK) cells）的作用仍不明确。因此，本研究采用一系列免疫学方法，探究骨化三醇对NK细胞的抗衰老及免疫调节作用，以阐明其在固有免疫中的重要功能。研究发现，骨化三醇可逆转NK细胞中衰老相关生物标志物的表达，并通过将细胞阻滞于G1期抑制其增殖，且不会引发细胞凋亡与耗竭。骨化三醇可抑制炎症相关细胞因子的释放，包括白细胞介素-5（IL-5）、白细胞介素-13（IL-13）、干扰素-γ（IFN-γ）及肿瘤坏死因子-α（TNF-α）。当NK细胞与K562肿瘤细胞共培养时，骨化三醇可下调其脱颗粒功能。本研究还发现，骨化三醇通过激活维生素D受体（VDR），上调衰老相关的沉默信息调节因子1-蛋白激酶R样内质网激酶（SIRT1/pERK）通路及SIRT1-ΔExon8（SIRT1-deltaExon8）的表达。此外，骨化三醇或可作为氧化应激诱导的NK细胞凋亡及线粒体失活的潜在负调控因子。综上，骨化三醇可通过激活SIRT1-PERK轴并抵抗氧化衰老，在体外（in vitro）环境中对人NK细胞发挥抗衰老作用。

搜集汇总

背景与挑战

背景概述

该数据集源自一项体外研究，探讨骨化三醇（维生素D的活性形式）对人类自然杀伤细胞的抗衰老作用。研究发现骨化三醇通过激活维生素D受体，上调SIRT1/pERK通路和SIRT1-ΔExon8表达，逆转衰老相关生物标志物、抑制细胞扩增和炎症因子释放，从而抵抗氧化衰老。数据集包含相关实验数据，支持骨化三醇作为NK细胞抗衰老潜在调节剂的研究。