Downregulated expression of miR-142-3p in macrophages contributes to increased IL-6 levels in aged mice. (December 2016)

• Record Type: Journal Article
• Authors: Liu, Yin; Song, Xiaoqi; Meng, Shu; Jiang, Minghong
• Is Part Of: Molecular immunology. Volume 80(2016:Dec.)
• Page Start: 11
• Page End: 16
• Publication Date: 2016-12
• Subjects: miR-142-3p -- IL-6 -- Aging -- Macrophage; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2016.10.009
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: MiR-142-3p is lowly expressed in the aged mice and does not respond to LPS stimulation. The stimulations of LPS, CpG or poly(I:C) significantly elevated the expression level of miR-142-3p in macrophages. miR-142-3p selectively targeted mouse IL-6 expression in macrophages. The suppression of miR-142-3p by histone deacetylation resulted in miR-142-3p lack of response to LPS stimulation in macrophages of aged mice. Abstract: Macrophages are innate immune cells that are important contributors to age-related functional impairment of the immune system. During the cell aging process, microRNAs are differentially expressed and participate in the regulation of aging-related immune responses. However, the role of aging-associated changes in miRNA expression in macrophages remains unclear. Here, we found that miR-142-3p expression is downregulated 50% in peritoneal macrophages from aged mice compared with young mice and is not upregulated by cell treatment with lipopolysaccharide (LPS), CpG, or polyinosinic-polycytidylic acid. Serum levels of miR-142-3p are also lower in aged mice than in young mice by q-PCR. Luciferase reporter analysis showed that IL-6 is a target of miR-142-3p in macrophages. In addition, the histone deacetylase inhibitor trichostatin A increased miR-142-3p expression by more than 3-fold in LPS-treated macrophages from aged mice compared with young mice, which in turn suppressed LPS-stimulated IL-6 production, suggesting that inhibition of miR-142-3p by histone deacetylation may be involved in the lack of response to LPS stimulation in macrophages of aged mice. These findings suggest that downregulation of miR-142-3p in macrophages of aged mice might contribute to IL-6-associated aging disorders and that epigenetic modification might be involved in age-related inflammatory diseases.