Cited by 126Immune Response and InflammationMicroRNA in disease regulationInflammasome and immune disorders

MicroRNA-92a Negatively Regulates Toll-like Receptor (TLR)-triggered Inflammatory Response in Macrophages by Targeting MKK4 Kinase

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Lai, Lihua, Song, Yinjing, Liu, Yang, Chen, Qingyun, Han, Quan, Chen, Weilin, Pan, Ting, Zhang, Yuanyuan +2 more·2013·Journal of Biological Chemistry

Abstract

Toll-like receptors (TLRs) play a critical role in the initiation of immune responses against invading pathogens. MicroRNAs have been shown to be important regulators of TLR signaling. In this study, we have found that the stimulation of multiple TLRs rapidly reduced the levels of microRNA-92a (miRNA-92a) and some other members of the miRNA-92a family in macrophages. miR-92a mimics significantly decreased, whereas miR-92a knockdown increased, the activation of the JNK/c-Jun pathway and the production of inflammatory cytokines in macrophages when stimulated with ligands for TLR4. Furthermore, mitogen-activated protein kinase kinase 4 (MKK4), a kinase that activates JNK/stress-activated protein kinase, was found to be directly targeted by miR-92a. Similar to the effects of the miR-92a mimics, knockdown of MKK4 inhibited the activation of JNK/c-Jun signaling and the production of TNF-α and IL-6. In conclusion, we have demonstrated that TLR-mediated miR-92a reduction feedback enhances TLR-triggered production of inflammatory cytokines in macrophages, thus outlining new mechanisms for fine-tuning the TLR-triggered inflammatory response.

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  • Silencing miR-92a increases JNK/c-Jun activation and pro-inflammatory cytokine production in macrophages.

    “silencing of miR-92a increases the activation of the JNK/c-Jun pathway and stimulates the production of pro-inflammatory cytokines in macrophages [134]”

    From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [134]

    The miR-92a Regulates TLR-triggered Inflammatory Response section reports that miR-92a inhibitors increased JNK and c-Jun phosphorylation and LPS-induced TNFα and IL-6 production in macrophages (Figs. 4C and 3E–F). The citing sentence omits the LPS/TLR-stimulation condition under which these effects were shown. (LLM, conf=0.82)

    Experimental — accuracy not yet measured
  • TLR stimulation downregulates miR-92a, which targets MKK4.

    “Stimulation of different TLRs downregulates miR-92a, which targets mitogen-activated protein kinase 4 (MKK4).”

    From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [134]

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Authors
Lai, L., Song, Y., Liu, Y., Chen, Q., Han, Q., Chen, W., Pan, T., Zhang, Y., Cao, X., & Wang, Q.
Affiliations
  • Zhejiang University (CN)
  • Second Military Medical University (CN)
Corresponding author
Wang, Qingqing
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2013-03
Volume
288
Issue
11
Pages
7956-7967
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1982263285
Cited by
126
References
65
Citations by year
2026: 2 · 2025: 5 · 2023: 6 · 2022: 6 · 2021: 10 · 2020: 16 · 2019: 8 · 2018: 16 · 2017: 14 · 2016: 13 · 2015: 13 · 2014: 7 · 2013: 10
FWCI
7.93
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
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-92a, TLR4, macrophages, MKK4, JNK/c-Jun signaling, inflammatory cytokines, TNF-α, interleukin-6
MeSH terms
Animals, Humans, Inflammation, Ligands, Macrophages, Mice, Inbred C57BL, Signal Transduction, Gene Expression Regulation, Enzymologic, Mice, Knockout, 3' Untranslated Regions, RNA, Small Interfering, MicroRNAs, MAP Kinase Kinase 4, Toll-Like Receptor 4, Mice

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