Institute of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Poland; Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Poland.
Institute of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Poland; Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Poland.
Mol Cell Endocrinol. 2018 Jul 15;470:1-13. doi: 10.1016/j.mce.2017.05.003. Epub 2017 May 3.
In this study, we provide a new evidence on immunosenescent-like phenotype induction in low density monocytes due to the long-term treatment with lipopolysaccharide (LPS). We show that LPS caused oxidative and nitrosative stress through zinc downregulation and calcium accumulation. In turn, increased amounts of ROS/RNS and pro-inflammatory cytokines TNFα, IL-1β, IL-6 led to the irreversible DNA damage, persistent DDR activation, proliferation inhibition, reduction in cell growth and immune impairment. Furthermore, we provide evidence that klotho reduced levels of ROS/RNS and pro-inflammatory cytokines as well as upregulated secretion of anti-inflammatory IL-10 in LPS-treated monocytes, thus the observed DNA damage was less severe, promptly and properly fixed and cells quickly resumed normal proliferation and maintained their immune functionality. Therefore, klotho protein could be considered as a protective factor against immunosenescent-like phenotype in monocytes an issue relevant to many immune disorders.
在这项研究中，我们提供了新的证据，表明长期使用脂多糖（LPS）会导致低密度单核细胞出现免疫衰老样表型。我们表明，LPS 通过锌下调和钙积累引起氧化和硝化应激。反过来，ROS/RNS 和促炎细胞因子 TNFα、IL-1β、IL-6 的增加量导致不可逆转的 DNA 损伤、持续的 DDR 激活、增殖抑制、细胞生长减少和免疫损伤。此外，我们提供的证据表明，klotho 降低了 ROS/RNS 和促炎细胞因子的水平，并上调了 LPS 处理单核细胞中抗炎性 IL-10 的分泌，因此观察到的 DNA 损伤不那么严重，迅速而恰当地固定，细胞很快恢复正常增殖并保持其免疫功能。因此，klotho 蛋白可以被认为是一种针对单核细胞免疫衰老样表型的保护因子，这是一个与许多免疫紊乱相关的问题。
