title: Downregulated expression of miR-142-3p in macrophages contributes to increased IL-6 levels in 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.
authors: National Key Laboratory of Medical Molecular Department of Immunology, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100005, China.
authors: Yin
authors: Y
authors: Liu
authors: National Key Laboratory of Medical Molecular Department of Immunology, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100005, China.
authors: Xiaoqi
authors: X
authors: Song
authors: National Key Laboratory of Medical Molecular Department of Immunology, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100005, China. Electronic address: mengshu129@163.com.
authors: Shu
authors: S
authors: Meng
authors: National Key Laboratory of Medical Molecular Department of Immunology, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100005, China. Electronic address: jiangminghong@163.com.
authors: Minghong
authors: M
authors: Jiang
mesh_terms: D000375:Aging / Q000235:genetics* / Q000276:immunology*; D000818:Animals; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000096:biosynthesis* / Q000276:immunology; D011070:Poly I-C / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D035683:MicroRNAs; C529102:Mirn142 microRNA, mouse; C577686:interleukin-6, mouse; D011070:Poly I-C
keywords: Aging; IL-6; Macrophage; miR-142-3p