Abstract
miR-181a has been presumed to target the 3'-untranslated regions (3'-UTR) of IL1a based on software predictions. miR-181a and IL1a have opposite expression levels in monocytes and macrophages in the inflammatory state. This led us to suspect that mir-181a has an important function in regulating inflammatory response by targeting IL1a. Fluorescence reporter assays showed that miR-181a effectively binds to the 3'-UTR of IL1a. The anti-inflammatory functions of miR-181a were investigated in lipopolysaccharides (LPS)-induced Raw264.7 and phorbol 12-myristate 13-acetate (PMA)/LPS-induced THP-1 cells. We found that miR-181a mimics significantly lowered IL1a expression levels in these cells and, interestingly, miR-181a inhibitors reversed this decrease. In addition, miR-181a mimics significantly inhibited increase in the levels of inflammatory factors (IL1b, IL6, and TNFa) in these cells. Furthermore, miR-181a mimics and inhibitors decreased and increased, respectively, production of reactive oxygen species in PMA/LPS-induced THP-1 cells. These results indicate that miR-181a regulates inflammatory responses by directly targeting the 3'-UTR of IL1a and down-regulating IL1a levels. Interestingly, we found that miR-181a inhibited production of inflammatory factors even in IL1a-induced THP-1 cells, suggesting that the anti-inflammatory effects of miR-181a possibly involves other targets in addition to IL1a. Thus, we provide the first evidence for anti-inflammatory effects of miR-181a mediated at least in part by down-regulating IL1a.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3' Untranslated Regions / genetics
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Animals
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Base Sequence
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Binding Sites
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Cell Line, Tumor
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Gene Expression Regulation / drug effects
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Humans
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Inflammation / genetics
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Inflammation / metabolism
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Interleukin-1alpha / deficiency
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Interleukin-1alpha / genetics
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Interleukin-1alpha / metabolism
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Interleukin-1beta / genetics
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Interleukin-1beta / metabolism
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Interleukin-6 / genetics
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Interleukin-6 / metabolism
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Lipopolysaccharides / pharmacology
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Macrophages / drug effects
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Macrophages / metabolism*
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Mice
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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Monocytes / drug effects
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Monocytes / metabolism*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA, Small Interfering / genetics
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Reactive Oxygen Species / metabolism
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Tetradecanoylphorbol Acetate / pharmacology
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
Substances
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3' Untranslated Regions
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IL1A protein, human
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IL1B protein, human
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Interleukin-1alpha
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Interleukin-1beta
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Interleukin-6
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Lipopolysaccharides
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MIrn181 microRNA, human
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MicroRNAs
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RNA, Messenger
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RNA, Small Interfering
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Reactive Oxygen Species
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Tumor Necrosis Factor-alpha
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Tetradecanoylphorbol Acetate
Grants and funding
This study was supported by the National Natural Science Foundation of China (81072680), the Guangdong Natural Science Foundation (10151805702000002), the Specialized Research Fund for the Doctoral Program of Higher Education of China (20100002120017), and the Shenzhen Science and Technology R&D Foundation (ZYC201105170341A). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.