Cited by 260MicroRNA in disease regulationImmune cells in cancerImmune Response and Inflammation

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miR-125a-5p Regulates Differential Activation of Macrophages and Inflammation

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Banerjee, Sami, Cui, Huachun, Xie, Na, Tan, Zheng, Yang, Shanzhong, Icyuz, Mert, Thannickal, Victor John, Abraham, Edward, Liu, Gang·2013·Journal of Biological Chemistry

DOI 10.1074/jbc.m112.426866PMC PMC3853290

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Abstract

Macrophage activation is a central event in immune responses. Macrophages undergoing classical activation (M1 macrophages) are proinflammatory, whereas alternatively activated macrophages (M2 macrophages) are generally anti-inflammatory. miRNAs play important regulatory roles in inflammatory response. However, the manner in which miRNAs regulate macrophage activation in response to different environmental cues has not been well defined. In this study, we found that M-BMM macrophages (M2) express greater levels of miR-125a-5p than do GM-BMM macrophages (M1). Stimulation of macrophages through TLR2 and TLR4 but not through TLR3 enhanced miR-125a-5p expression. Up-regulation of miR-125a-5p after TLR2/4 activation requires the adaptor MYD88 but not TRIF. Overexpression of miR-125a-5p diminished M1 phenotype expression induced by LPS but promoted M2 marker expression induced by IL-4. In contrast, knockdown of miR-125a-5p promoted M1 polarization and diminished IL-4-induced M2 marker expression. We found that miR-125a-5p targets KLF13, a transcriptional factor that has an important role in T lymphocyte activation and inflammation. KLF13 knockdown had similar effects on M1 activation as did miR-125a-5p overexpression. In addition, miR-125a-5p regulates phagocytic and bactericidal activities of macrophages. Our data suggest that miR-125a-5p has an important role in suppressing classical activation of macrophages while promoting alternative activation.

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Authors: Banerjee, S., Cui, H., Xie, N., Tan, Z., Yang, S., Icyuz, M., Thannickal, V. J., Abraham, E., & Liu, G.
Affiliations: University of Alabama at Birmingham (US)
Wake Forest University Health Sciences (US)
Corresponding author: Liu, Gang
ORCID: Banerjee, Sami
Xie, Na
Tan, Zheng
Yang, Shanzhong
Icyuz, Mert
Thannickal, Victor John
Abraham, Edward
Liu, Gang
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2013-12
Volume: 288
Issue: 49
Pages: 35428-35436
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m112.426866
PMC: PMC3853290
OpenAlex: W1989029018
Cited by: 258
References: 52
Citations by year: 2026: 10 · 2025: 12 · 2024: 19 · 2023: 25 · 2022: 29 · 2021: 33 · 2020: 17 · 2019: 25 · 2018: 24 · 2017: 19 · 2016: 21 · 2015: 14 · 2014: 9
FWCI: 5.16
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 2480 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Heart, Lung, and Blood Institute (HL 076206, HL114470, HL-105473, R01HL105473, R01HL076206, P01HL114470)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR048311)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: miR-125a-5p, macrophage polarization, M1 macrophages, M2 macrophages, classical activation, alternative activation, KLF13, TLR2, TLR4, MyD88, TRIF, LPS, IL-4, inflammation, phagocytosis, bactericidal activity, bone marrow-derived macrophages
MeSH terms: Animals, Escherichia coli, Inflammation, Macrophage Activation, Macrophages, Mice, Inbred C57BL, Repressor Proteins, Up-Regulation, Mice, Knockout, Cell Cycle Proteins, Adaptor Proteins, Vesicular Transport, MicroRNAs, Toll-Like Receptor 2, Toll-Like Receptor 4, Mice, Kruppel-Like Transcription Factors, Myeloid Differentiation Factor 88, Gene Knockdown Techniques

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miR-125a-5p Regulates Differential Activation of Macrophages and Inflammation

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