Dysregulated expression of miR-146a contributes to age-related dysfunction of macrophages.

摘要: Summary Age-associated immune dysfunction, characterized by increased systemic levels of cytokines, manifests as an susceptibility to infections. Thus, understanding these negative regulators the response has paved way delineating signaling pathways that impact senescence. In present study, we found miR-146a, which negatively regulated expression IL-1β and IL-6, was highly expressed in aged mice. However, there a lack stimulation lipopolysaccharide (LPS) proinflammatory cytokines macrophages As result, feedback regulation loop with miR-146a involving down-regulation inflammation factors interrupted Aberrant NF-κB binding promoter demonstrated be associated abnormal The DNA methyltransferase inhibitor (5-aza-2-deoxycytidine) histone deacetylase [trichostatin A (TSA)] both significantly up-regulated transcriptional activation altering DNA-binding activity isolated from mice, suggests methylation acetylation are involved suppression age-dependent expression. Additionally, high (HDACs) expressions contributed inhibition LPS-stimulated mice vitro. While HDACs activities TSA could improve LPS-induced inflammatory responses owing up-regulation These data indicate dysregulated results age-associated dysfunction macrophages, may good target for treatment age-related diseases.