The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.
Secreted protein lipocalin‐2 promotes microglial M1 polarization
Abstract
Activated macrophages are classified into two different forms: classically activated (M1) or alternatively activated (M2) macrophages. The presence of M1/M2 phenotypic polarization has also been suggested for microglia. Here, we report that the secreted protein lipocalin 2 (LCN2) amplifies M1 polarization of activated microglia. LCN2 protein (EC 50 1 μg/ml), but not glutathione S ‐transferase used as a control, increased the M1‐related gene expression in cultured mouse microglial cells after 8–24 h. LCN2 was secreted from M1‐polarized, but not M2‐polarized, microglia. LCN2 inhibited phosphorylation of STAT6 in IL‐4‐stimulated microglia, suggesting LCN2 suppression of the canonical M2 signaling. In the lipopolysaccharide (LPS)‐induced mouse neuroinflammation model, the expression of LCN2 was notably increased in microglia. Primary microglial cultures derived from LCN2‐deficient mice showed a suppressed M1 response and enhanced M2 response. Mice lacking LCN2 showed a markedly reduced M1‐related gene expression in microglia after LPS injection, which was consistent with the results of histological analysis. Neuroinflammation‐associated impairment in motor behavior and cognitive function was also attenuated in the LCN2‐deficient mice, as determined by the rotarod performance test, fatigue test, open‐field test, and object recognition task. These findings suggest that LCN2 is an M1‐amplifier in brain microglial cells.—Jang, E., Lee, S., Kim, J.‐H., Kim, J.‐H., Seo, J.‐W., Lee, W.‐H., Mori, K., Nakao, K., Suk, K. Secreted protein lipocalin‐2 promotes microglial M1 polarization. FASEB J. 27, 1176–1190 (2013). www.fasebj.org
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“M2 depletion caused an increase in the number and proportion of iNOS+ M1 cells (Fig. 5d and Supplementary Fig. 8g online), supporting previous findings of reciprocal regulation between M1 and M2 polarization and associated cytokines25, 26.”
From M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination (2013) · cites this paper as [26]
Citations
Cites
Exploring the full spectrum of macrophage activation
Mosser, D. M., & Edwards, J. P. (2008) · Nature Reviews Immunology · doi:10.1038/nri2448 · Cited by 9,144
MANTOVANI, A., SOZZANI, S., LOCATI, M., ALLAVENA, P., & SICA, A. (2002) · Trends in Immunology · doi:10.1016/s1471-4906(02)02302-5 · Cited by 5,528
Protective and pathogenic functions of macrophage subsets
Murray, P. J., & Wynn, T. A. (2011) · Nature Reviews Immunology · doi:10.1038/nri3073 · Cited by 5,269
Monocyte and macrophage heterogeneity
Gordon, S., & Taylor, P. R. (2005) · Nature Reviews Immunology · doi:10.1038/nri1733 · Cited by 5,190
Microglia: Active sensor and versatile effector cells in the normal and pathologic brain
Hanisch, U.-K., & Kettenmann, H. (2007) · Nature Neuroscience · doi:10.1038/nn1997 · Cited by 3,676
Kettenmann, H., Hanisch, U.-K., Noda, M., & Verkhratsky, A. (2011) · Physiological Reviews · doi:10.1152/physrev.00011.2010 · Cited by 3,547
Development of Monocytes, Macrophages, and Dendritic Cells
Geissmann, F., Manz, M. G., Jung, S., Sieweke, M. H., Merad, M., & Ley, K. (2010) · Science · doi:10.1126/science.1178331 · Cited by 3,049
Alternative Activation of Macrophages: An Immunologic Functional Perspective
Martinez, F. O., Helming, L., & Gordon, S. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132532 · Cited by 2,745
Transcriptional regulation of macrophage polarization: enabling diversity with identity
Lawrence, T., & Natoli, G. (2011) · Nature Reviews Immunology · doi:10.1038/nri3088 · Cited by 2,284
Distinct role of macrophages in different tumor microenvironments
Lewis, C. E., & Pollard, J. W. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-4005 · Cited by 2,225
Research works printed but not linked: 1
- 10.4049/jimmunol.179.5.3231 · DOI
Cited by
Sorted by citations
M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination
Miron, V. E., Boyd, A., Zhao, J.-W., Yuen, T. J., Ruckh, J. M., Shadrach, J. L., van Wijngaarden, P., Wagers, A. J., Williams, A., Franklin, R. J. M., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3469 · Cited by 1,777
Microglial and macrophage polarization—new prospects for brain repair
Hu, X., Leak, R. K., Shi, Y., Suenaga, J., Gao, Y., Zheng, P., & Chen, J. (2015) · Nature Reviews Neurology · doi:10.1038/nrneurol.2014.207 · Cited by 1,366
Microglia in the TBI brain: The good, the bad, and the dysregulated
Loane, D. J., & Kumar, A. (2015) · Experimental Neurology · doi:10.1016/j.expneurol.2015.08.018 · Cited by 850
Zhou, D., Huang, C., Lin, Z., Zhan, S., Kong, L., Fang, C., & Li, J. (2014) · Cellular Signalling · doi:10.1016/j.cellsig.2013.11.004 · Cited by 778
Functions and mechanisms of microglia/macrophages in neuroinflammation and neurogenesis after stroke
Xiong, X., Liu, L., & Yang, Q. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.05.001 · Cited by 713
Metadata
- Authors
- Jang, E., Lee, S., Kim, J., Kim, J., Seo, J., Lee, W., Mori, K., Nakao, K., & Suk, K.
- Affiliations
- Kyungpook National University (KR)
- Kyoto University (JP)
- Corresponding author
- Suk, Kyoungho
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2012-12-03
- Volume
- 27
- Issue
- 3
- Pages
- 1176-1190
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2168114040
- Cited by
- 198
- References
- 66
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 13 · 2023: 20 · 2022: 19 · 2021: 19 · 2020: 11 · 2019: 8 · 2018: 11 · 2017: 12 · 2016: 19 · 2015: 16 · 2014: 21 · 2013: 11
- FWCI
- 7.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Science and Technology (2012‐0009328, 2008‐04090)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- neutrophil gelatinase-associated lipocalin, microglial M1 polarization, microglial M2 polarization, macrophage polarization, neuroinflammation, STAT6 phosphorylation, IL-4 signaling, lipopolysaccharide, cognitive impairment, secreted proteins
- MeSH terms
- Lipocalin-2, Acute-Phase Proteins, Animals, Gene Expression Regulation, Humans, Inflammation, Lipopolysaccharides, Mice, Mutant Strains, Phosphorylation, Proto-Oncogene Proteins, Oncogene Proteins, Cell Polarity, Microglia, Jurkat Cells, STAT6 Transcription Factor, Mice, Lipocalins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
