MiR-350-3p Contributes to Age-Associated Impairment of IL-6 Production by Macrophages

Abstract

ABSTRACTAging-associated dysfunction of the immune system contributes to the increase in pathophysiological processes that occur with age. Numerous studies have shown that microRNAs regulate immune responses, although their role in age-related macrophage dysfunction remains elusive. Here, we found that miR-350-3p is expressed at lower levels in peritoneal macrophages from aged mice compared with young mice, and that lipopolysaccharide (LPS) stimulation downregulates miR-350-3p expression to a greater extent in young macrophages compared with aged macrophages. Consequently, LPS-stimulated aged macrophages express more miR-350-3p than do similarly treated young macrophages. Luciferase reporter assays showed that interleukin (IL)-6 mRNA is a miR-350-3p target in macrophages. Furthermore, although LPS induces less IL-6 production by aged macrophages than by young macrophages, the aged cell response is rescued by production miR-350-3p inhibition. These findings suggest that miR-350-3p may contribute to age-related impairment of macrophage function and could be a novel target for the treatment of age-related inflammatory diseases.