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Cited by 215MicroRNA in disease regulationImmune Response and InflammationNeuroinflammation and Neurodegeneration Mechanisms

IL-10–induced microRNA-187 negatively regulates TNF-α, IL-6, and IL-12p40 production in TLR4-stimulated monocytes

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Rossato, Marzia, Curtale, Graziella, Tamassia, Nicola, Castellucci, Monica, Mori, Laura, Gasperini, Sara, Mariotti, Barbara, De Luca, Mariacristina +4 more·2012·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1209100109PMC PMC3494907
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Abstract

IL-10 is a potent anti-inflammatory molecule that, in phagocytes, negatively targets cytokine expression at transcriptional and posttranscriptional levels. Posttranscriptional checkpoints also represent the specific target of a recently discovered, evolutionary conserved class of small silencing RNAs known as “microRNAs” (miRNAs), which display the peculiar function of negatively regulating mRNA processing, stability, and translation. In this study, we report that activation of primary human monocytes up-regulates the expression of miR-187 both in vitro and in vivo. Accordingly, we identify miR-187 as an IL-10–dependent miRNA playing a role in IL-10–mediated suppression of TNF-α, IL-6, and the p40 subunit of IL-12 (IL-12p40) produced by primary human monocytes following activation of Toll-like receptor 4 (TLR4). Ectopic expression of miR-187 consistently and selectively reduces TNFα, IL-6, and IL-12p40 produced by LPS-activated monocytes. Conversely, the production of LPS-induced TNF-α, IL-6, and IL-12p40 is increased significantly when miR-187 expression is silenced. Our data demonstrate that miR-187 directly targets TNF-α mRNA stability and translation and indirectly decreases IL-6 and IL-12p40 expression via down-modulation of IκBζ, a master regulator of the transcription of these latter two cytokines. These results uncover an miRNA-mediated pathway controlling cytokine expression and demonstrate a central role of miR-187 in the physiological regulation of IL-10–driven anti-inflammatory responses.

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  • miR-187 participates in IL-10-mediated suppression of TNF-α, IL-6, and IL-12 p40 release upon TLR4 activation by LPS.

    “MiR-187 was shown to take part in IL-10-mediated suppression of TNF-α, IL-6, and the p40 subunit of IL-12 release upon TLR4 activation by LPS [223].”

    From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [223]

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Authors
Rossato, M., Curtale, G., Tamassia, N., Castellucci, M., Mori, L., Gasperini, S., Mariotti, B., De Luca, M., Mirolo, M., Cassatella, M. A., Locati, M., & Bazzoni, F.
Affiliations
  • University of Verona (IT)
  • University of Milan (IT)
  • Department of Medical Biotechnologies and Translational Medicine, University of Milan, 20089 Rozzano (Milan), Italy; and
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2012-10-03
Volume
109
Issue
45
Pages
E3101-10
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1209100109
PMC
PMC3494907
OpenAlex
W1985854258
Cited by
215
References
8
Citations by year
2026: 4 · 2025: 9 · 2024: 6 · 2023: 10 · 2022: 16 · 2021: 13 · 2020: 12 · 2019: 15 · 2018: 16 · 2017: 22 · 2016: 24 · 2015: 19 · 2014: 25 · 2013: 24
FWCI
7.22
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
Funders
  • Istituto Superiore di Sanità
  • Associazione Italiana per la Ricerca sul Cancro (IG‐11782)
  • Fondazione Cassa di Risparmio di Verona Vicenza Belluno e Ancona
  • Università degli Studi di Verona
  • Regione Lombardia
  • Alleanza Contro il Cancro
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
IL-10, TLR4, monocytes, TNF-α, interleukin-6, IL-12p40, IκB, post-transcriptional regulation, mRNA stability, lipopolysaccharide stimulation, anti-inflammatory signaling, cytokine expression
MeSH terms
Animals, Base Sequence, Humans, Lipopolysaccharides, Molecular Sequence Data, Monocytes, Nuclear Proteins, RNA, Messenger, Tumor Necrosis Factor-alpha, Down-Regulation, Interleukin-6, Up-Regulation, Interleukin-10, Sepsis, I-kappa B Proteins, MicroRNAs, Adaptor Proteins, Signal Transducing, Toll-Like Receptor 4, Mice, Interleukin-12 Subunit p40, Gene Knockdown Techniques, HEK293 Cells, Argonaute Proteins

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