Cited by 581Immune Response and InflammationMicroRNA in disease regulationNeuroinflammation and Neurodegeneration Mechanisms

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The Kinase Akt1 Controls Macrophage Response to Lipopolysaccharide by Regulating MicroRNAs

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Androulidaki, Ariadne, Iliopoulos, Dimitrios, Arranz, Alicia, Doxaki, Christina, Schworer, Steffen, Zacharioudaki, Vassiliki, Margioris, Andrew N., Tsichlis, Philip N., Tsatsanis, Christos·2009·Immunity

DOI 10.1016/j.immuni.2009.06.024PMC PMC2865583

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Abstract

MicroRNAs regulated by lipopolysaccharide (LPS) target genes that contribute to the inflammatory phenotype. Here, we showed that the protein kinase Akt1, which is activated by LPS, positively regulated miRNAs let-7e and miR-181c but negatively regulated miR-155 and miR-125b. In silico analyses and transfection studies revealed that let-7e repressed Toll-like receptor 4 (TLR4), whereas miR-155 repressed SOCS1, two proteins critical for LPS-driven TLR signaling, which regulate endotoxin sensitivity and tolerance. As a result, Akt1(-/-) macrophages exhibited increased responsiveness to LPS in culture and Akt1(-/-) mice did not develop endotoxin tolerance in vivo. Overexpression of let-7e and suppression of miR-155 in Akt1(-/-) macrophages restored sensitivity and tolerance to LPS in culture and in animals. These results indicate that Akt1 regulates the response of macrophages to LPS by controlling miRNA expression.

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Authors: Androulidaki, A., Iliopoulos, D., Arranz, A., Doxaki, C., Schworer, S., Zacharioudaki, V., Margioris, A. N., Tsichlis, P. N., & Tsatsanis, C.
Affiliations: University of Crete (GR)
Harvard University (US)
Tufts Medical Center (US)
Corresponding author: Tsatsanis, Christos
ORCID: Iliopoulos, Dimitrios
Tsichlis, Philip N.
Tsatsanis, Christos
Venue: Immunity
Publisher: Elsevier BV
Published: 2009-08
Volume: 31
Issue: 2
Pages: 220-231
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2009.06.024
PMC: PMC2865583
OpenAlex: W2067647130
Cited by: 581
References: 46
Citations by year: 2026: 14 · 2025: 13 · 2024: 17 · 2023: 22 · 2022: 28 · 2021: 26 · 2020: 27 · 2019: 25 · 2018: 42 · 2017: 42 · 2016: 50 · 2015: 47 · 2014: 45 · 2013: 54 · 2012: 53
FWCI: 18.41
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 1446 d)
Locations: Immunity (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Cancer Institute (R01CA057436, N02 CO041101, 2-CO-41101)
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 › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: AKT1, macrophages, lipopolysaccharide, microRNA, let-7e, miR-155, miR-181c, miR-125b, TLR4, SOCS1, endotoxin tolerance, endotoxin sensitivity, LPS signaling, inflammation
MeSH terms: Suppressor of Cytokine Signaling 1 Protein, Animals, Cell Line, Immune Tolerance, Lipopolysaccharides, Macrophages, Mice, Inbred C57BL, Mice, Knockout, MicroRNAs, Suppressor of Cytokine Signaling Proteins, Proto-Oncogene Proteins c-akt, Toll-Like Receptor 4, Mice

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The Kinase Akt1 Controls Macrophage Response to Lipopolysaccharide by Regulating MicroRNAs

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