Klotho protects human monocytes from LPS-induced immune impairment associated with immunosenescent-like phenotype

Abstract

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.

Keywords: Cytotoxicity; Genotoxicity; Immunosenescence; Klotho; LPS; Monocytes.