The DOI matches its Crossref record; 45 of the 46 references it cites were found in a registry or an index.
The Kinase Akt1 Controls Macrophage Response to Lipopolysaccharide by Regulating MicroRNAs
Open accessAbstract
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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“Macrophage development is regulated by miR-155 and miR-146a expression [54,55,56,57].”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [57]
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“They showed that let-7e targets TLR4 and miR-155 targets SOCS1, thus leading to LPS tolerance [57].”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [57]
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“Protein kinase Akt1 upregulates let-7e and miR-181c but downregulates miR-155 and miR-125b.”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [57]
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“Interestingly, miR-155 is also repressed by IL-10 signaling through STAT3 [57].”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [57]
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Cites
MicroRNA-155 is induced during the macrophage inflammatory response
O'Connell, R. M., Taganov, K. D., Boldin, M. P., Cheng, G., & Baltimore, D. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610731104 · Cited by 1,866
Cho, H., Mu, J., Kim, J. K., Thorvaldsen, J. L., Chu, Q., Crenshaw, E. B., Kaestner, K. H., Bartolomei, M. S., Shulman, G. I., & Birnbaum, M. J. (2001) · Science · doi:10.1126/science.292.5522.1728 · Cited by 1,860
IRAK-M Is a Negative Regulator of Toll-like Receptor Signaling
Kobayashi, K. S., Hernandez, L. D., Galán, J. E., Janeway, C. A., Medzhitov, R. M., & Flavell, R. A. (2002) · Cell · doi:10.1016/s0092-8674(02)00827-9 · Cited by 1,310
Tili, E., Michaille, J.-J., Cimino, A., Costinean, S., Dumitru, C. D., Adair, B., Fabbri, M., Alder, H., Liu, C. G., Calin, G. A., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.8.5082 · Cited by 1,304
Martin, M., Rehani, K., Jope, R. S., & Michalek, S. M. (2005) · Nature Immunology · doi:10.1038/ni1221 · Cited by 1,099
MicroRNAs: new regulators of immune cell development and function
Baltimore, D., Boldin, M., O’Connell, R. M., Rao, D. S., & Taganov, K. D. (2008) · Nature Immunology · doi:10.1038/ni.f.209 · Cited by 1,097
MicroRNA Control in the Immune System: Basic Principles
Xiao, C., & Rajewsky, K. (2009) · Cell · doi:10.1016/j.cell.2008.12.027 · Cited by 1,020
Thum, T., Galuppo, P., Wolf, C., Fiedler, J., Kneitz, S., Laake, L. W. V., Doevendans, P. A., Mummery, C. L., Borlak, J. T., Haverich, A., et al. (2007) · Circulation · doi:10.1161/circulationaha.107.687947 · Cited by 890
Inositol phosphatase SHIP1 is a primary target of miR-155
O'Connell, R. M., Chaudhuri, A. A., Rao, D. S., & Baltimore, D. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0902636106 · Cited by 826
TNF-α Induction by LPS Is Regulated Posttranscriptionally via a Tpl2/ERK-Dependent Pathway
Dumitru, C. D., Ceci, J. D., Tsatsanis, C., Kontoyiannis, D. L., Stamatakis, K., Lin, J., Patriotis, C., Jenkins, N. A., Copeland, N. G., Kollias, G. A., et al. (2000) · Cell · doi:10.1016/s0092-8674(00)00210-5 · Cited by 810
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Alternative activation of macrophages: mechanism and functions
Gordon, S., & Martinez, F. O. (2010) · Immunity · doi:10.1016/j.immuni.2010.05.007 · Cited by 4,197
Diversity, Mechanisms, and Significance of Macrophage Plasticity
Locati, M., Curtale, G., & Mantovani, A. (2020) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-012418-012718 · Cited by 2,199
Physiological and pathological roles for microRNAs in the immune system
O'Connell, R. M., Rao, D. S., Chaudhuri, A. A., & Baltimore, D. (2010) · Nature Reviews Immunology · doi:10.1038/nri2708 · Cited by 1,378
Akt Signaling Pathway in Macrophage Activation and M1/M2 Polarization
Vergadi, E., Ieronymaki, E., Lyroni, K., Vaporidi, K., & Tsatsanis, C. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1601515 · Cited by 1,148
Self-citationFunction of miR-146a in Controlling Treg Cell-Mediated Regulation of Th1 Responses
Lu, L.-F., Boldin, M. P., Chaudhry, A., Lin, L.-L., Taganov, K. D., Hanada, T., Yoshimura, A., Baltimore, D., & Rudensky, A. Y. (2010) · Cell · doi:10.1016/j.cell.2010.08.012 · Cited by 849
Metadata
- 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
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2009-08
- Volume
- 31
- Issue
- 2
- Pages
- 220-231
- ISSN
- 1074-7613 (ISSN-L)
- 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
- 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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