miR-147, a microRNA that is induced upon Toll-like receptor stimulation, regulates murine macrophage inflammatory responses
Open accessAbstract
Toll-like receptors (TLRs) are major receptors that enable inflammatory cells to recognize invading microbial pathogens. MicroRNAs are small non-coding RNAs that play important regulatory roles in a variety of biological processes. In this study, we found that a microRNA, miR-147, was induced upon stimulation of multiple TLRs and functioned as a negative regulator of TLR-associated signaling events in murine macrophages. We first demonstrated that the NMES1 transcript was a functional primary miR-147. miR-147 was induced in LPS-stimulated mouse macrophages and under in vivo conditions in the lungs of LPS-treated mice. Expression of miR-147 was greater after cellular activation by TLR4 than after engagement of either TLR2 or TLR3, suggesting that maximal induction of miR-147 required activation of both NF-κB and IRF3. TLR4-induced miR-147 expression was both MyD88- and TRIF-dependent. The miR-147 promoter was responsive to TLR4 stimulation and both NF-κB and STAT1α bound to the miR-147 promoter. miR-147 mimics or induced expression of miR-147 decreased, whereas miR-147 knockdown increased inflammatory cytokine expression in macrophages stimulated with ligands to TLR2, TLR3, and TLR4. These data demonstrate a negative-feedback loop in which TLR stimulation induces miR-147 to prevent excessive inflammatory responses.
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In murine macrophages, stimulation of TLR2, TLR3, and TLR4 upregulates miR-147 via NF-κB (+/− IRF3), which suppresses TNF-α and IL-6.
“In murine macrophage stimulation of multiple TLRs, namely TLR2, TLR3, and TLR4 by PAM3CSK4, poly(I:C), and LPS, respectively, upregulates miR-147 through NF-κB (+/− IRF3), which suppresses proinflammatory cytokines, such as TNF-α and IL-6 [208].”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [208]
miR-147 is induced upon TLR stimulation and regulates murine macrophage inflammatory responses.
“The microglial cell-line enriched cluster contained 20 miRNAs including miR-146a and a number of other miRNAs reportedly involved in inflammation, such as miR-155, miR-221 [23] and miR-147, a microRNA that is induced upon Toll-like receptor (TLR) stimulation and regulates murine macrophage inflammatory responses [24].”
From MicroRNA 146a (miR-146a) Is Over-Expressed during Prion Disease and Modulates the Innate Immune Response and the Microglial Activation State (2012) · cites this paper as [24]
The microglial cell-line enriched cluster contained 20 miRNAs including miR-146a and other inflammation-related miRNAs such as miR-155, miR-221 and miR-147.
“The microglial cell-line enriched cluster contained 20 miRNAs including miR-146a and a number of other miRNAs reportedly involved in inflammation, such as miR-155, miR-221 [23] and miR-147, a microRNA that is induced upon Toll-like receptor (TLR) stimulation and regulates murine macrophage inflammatory responses [24].”
From MicroRNA 146a (miR-146a) Is Over-Expressed during Prion Disease and Modulates the Innate Immune Response and the Microglial Activation State (2012) · cites this paper as [24]
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- Authors
- Liu, G., Friggeri, A., Yang, Y., Park, Y.-J., Tsuruta, Y., & Abraham, E.
- Affiliations
- University of Alabama at Birmingham (US)
- Inserm (FR)
- Corresponding author
- Abraham, Edward
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-09-15
- Volume
- 106
- Issue
- 37
- Pages
- 15819-15824
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2747202
- OpenAlex
- W1977745306
- Cited by
- 438
- References
- 2
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 14 · 2023: 22 · 2022: 11 · 2021: 23 · 2020: 22 · 2019: 24 · 2018: 27 · 2017: 26 · 2016: 37 · 2015: 30 · 2014: 48 · 2013: 44 · 2012: 37
- FWCI
- 12.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL-62221, HL 76206, R01HL076206, R01HL062221)
- National Institute of General Medical Sciences (R01GM087748, GM87748)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK072482)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- microRNA, Toll-like receptors, macrophages, TLR4, TLR2, TLR3, LPS, NF-κB, IRF3, STAT1, MyD88, TRIF, negative feedback loop, inflammatory cytokines, lung inflammation
- MeSH terms
- Animals, Cell Line, Humans, Inflammation, Lipopolysaccharides, Macrophages, Mice, Inbred C57BL, Promoter Regions, Genetic, Up-Regulation, Macrophages, Alveolar, Mice, Knockout, Feedback, Physiological, MicroRNAs, Toll-Like Receptors, Toll-Like Receptor 4, Mice
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